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51. Supplemental Figure 2 from ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer–Containing Antibody–Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

Author

Flynn, Michael J., primary, Zammarchi, Francesca, primary, Tyrer, Peter C., primary, Akarca, Ayse U., primary, Janghra, Narinder, primary, Britten, Charles E., primary, Havenith, Carin E.G., primary, Levy, Jean-Noel, primary, Tiberghien, Arnaud, primary, Masterson, Luke A., primary, Barry, Conor, primary, D'Hooge, Francois, primary, Marafioti, Teresa, primary, Parren, Paul W.H.I., primary, Williams, David G., primary, Howard, Philip W., primary, van Berkel, Patrick H., primary, and Hartley, John A., primary

Published
2023
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52. Supplemental Figure 6 from ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer–Containing Antibody–Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

Author

Flynn, Michael J., primary, Zammarchi, Francesca, primary, Tyrer, Peter C., primary, Akarca, Ayse U., primary, Janghra, Narinder, primary, Britten, Charles E., primary, Havenith, Carin E.G., primary, Levy, Jean-Noel, primary, Tiberghien, Arnaud, primary, Masterson, Luke A., primary, Barry, Conor, primary, D'Hooge, Francois, primary, Marafioti, Teresa, primary, Parren, Paul W.H.I., primary, Williams, David G., primary, Howard, Philip W., primary, van Berkel, Patrick H., primary, and Hartley, John A., primary

Published
2023
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53. Supplemental Figure 4 from ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer–Containing Antibody–Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

Author

Flynn, Michael J., primary, Zammarchi, Francesca, primary, Tyrer, Peter C., primary, Akarca, Ayse U., primary, Janghra, Narinder, primary, Britten, Charles E., primary, Havenith, Carin E.G., primary, Levy, Jean-Noel, primary, Tiberghien, Arnaud, primary, Masterson, Luke A., primary, Barry, Conor, primary, D'Hooge, Francois, primary, Marafioti, Teresa, primary, Parren, Paul W.H.I., primary, Williams, David G., primary, Howard, Philip W., primary, van Berkel, Patrick H., primary, and Hartley, John A., primary

Published
2023
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54. Supplemental Figure 1 from ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer–Containing Antibody–Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

Author

Flynn, Michael J., primary, Zammarchi, Francesca, primary, Tyrer, Peter C., primary, Akarca, Ayse U., primary, Janghra, Narinder, primary, Britten, Charles E., primary, Havenith, Carin E.G., primary, Levy, Jean-Noel, primary, Tiberghien, Arnaud, primary, Masterson, Luke A., primary, Barry, Conor, primary, D'Hooge, Francois, primary, Marafioti, Teresa, primary, Parren, Paul W.H.I., primary, Williams, David G., primary, Howard, Philip W., primary, van Berkel, Patrick H., primary, and Hartley, John A., primary

Published
2023
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55. Supplementary Tables S1-S4 from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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56. Supplementary Figure 3 from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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57. Supplemental methods and tables from ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer–Containing Antibody–Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

Author

Flynn, Michael J., primary, Zammarchi, Francesca, primary, Tyrer, Peter C., primary, Akarca, Ayse U., primary, Janghra, Narinder, primary, Britten, Charles E., primary, Havenith, Carin E.G., primary, Levy, Jean-Noel, primary, Tiberghien, Arnaud, primary, Masterson, Luke A., primary, Barry, Conor, primary, D'Hooge, Francois, primary, Marafioti, Teresa, primary, Parren, Paul W.H.I., primary, Williams, David G., primary, Howard, Philip W., primary, van Berkel, Patrick H., primary, and Hartley, John A., primary

Published
2023
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58. Supplementary Figure 1 from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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59. Supplementary Data from Dynamic Changes in the NK-, Neutrophil-, and B-cell Immunophenotypes Relevant in High Metastatic Risk Post Neoadjuvant Chemotherapy–Resistant Early Breast Cancers

Author

Gazinska, Patrycja, primary, Milton, Charlotte, primary, Iacovacci, Jacopo, primary, Ward, Joseph, primary, Buus, Richard, primary, Alaguthurai, Thanussuyah, primary, Graham, Rosalind, primary, Akarca, Ayse, primary, Lips, Esther, primary, Naidoo, Kalnisha, primary, Wesseling, Jelle, primary, Marafioti, Teresa, primary, Cheang, Maggie, primary, Gillett, Cheryl, primary, Wu, Yin, primary, Khan, Aadil, primary, Melcher, Alan, primary, Salgado, Roberto, primary, Dowsett, Mitch, primary, Tutt, Andrew, primary, Roxanis, Ioannis, primary, Haider, Syed, primary, and Irshad, Sheeba, primary

Published
2023
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60. Supplementary Figure from Dynamic Changes in the NK-, Neutrophil-, and B-cell Immunophenotypes Relevant in High Metastatic Risk Post Neoadjuvant Chemotherapy–Resistant Early Breast Cancers

Author

Gazinska, Patrycja, primary, Milton, Charlotte, primary, Iacovacci, Jacopo, primary, Ward, Joseph, primary, Buus, Richard, primary, Alaguthurai, Thanussuyah, primary, Graham, Rosalind, primary, Akarca, Ayse, primary, Lips, Esther, primary, Naidoo, Kalnisha, primary, Wesseling, Jelle, primary, Marafioti, Teresa, primary, Cheang, Maggie, primary, Gillett, Cheryl, primary, Wu, Yin, primary, Khan, Aadil, primary, Melcher, Alan, primary, Salgado, Roberto, primary, Dowsett, Mitch, primary, Tutt, Andrew, primary, Roxanis, Ioannis, primary, Haider, Syed, primary, and Irshad, Sheeba, primary

Published
2023
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61. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

Author

McGranahan, Nicholas, Furness, Andrew J. S., Rosenthal, Rachel, Ramskov, Sofie, Lyngaa, Rikke, Saini, Sunil Kumar, Jamal-Hanjani, Mariam, Wilson, Gareth A., Birkbak, Nicolai J., Hiley, Crispin T., Watkins, Thomas B. K., Shafi, Seema, Murugaesu, Nirupa, Mitter, Richard, Akarca, Ayse U., Linares, Joseph, Marafioti, Teresa, Henry, Jake Y., Van Allen, Eliezer M., Miao, Diana, Schilling, Bastian, Schadendorf, Dirk, Garraway, Levi A., Makarov, Vladimir, Rizvi, Naiyer A., Snyder, Alexandra, Hellmann, Matthew D., Merghoub, Taha, Wolchok, Jedd D., Shukla, Sachet A., Wu, Catherine J., Peggs, Karl S., Chan, Timothy A., Hadrup, Sine R., Quezada, Sergio A., and Swanton, Charles

Published
2016

62. Thyroid MALT lymphoma: self-harm to gain potential T-cell help

Author

Wu, Fangtian, Watanabe, Natsuko, Tzioni, Maria-Myrsini, Akarca, Ayse, Zhang, Chunye, Li, Yan, Chen, Zi, Cucco, Francesco, Carmell, Natasha, Noh, Jaeduk Yoshimura, Ito, Koichi, Dobson, Rachel, Moody, Sarah, Yao, Wenqing, Zhang, Wenyan, Liu, Weiping, Liu, Hongxiang, Okosun, Jessica, Chott, Andreas, Bi, Yingwen, Chuang, Shih-Sung, Raderer, Markus, Li, Jian-Yong, Marafioti, Teresa, and Du, Ming-Qing

Abstract

The development of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is driven by chronic inflammatory responses and acquired genetic changes. To investigate its genetic bases, we performed targeted sequencing of 93 genes in 131 MALT lymphomas including 76 from the thyroid. We found frequent deleterious mutations of TET2(86%), CD274(53%), TNFRSF14(53%), and TNFAIP3(30%) in thyroid MALT lymphoma. CD274was also frequently deleted, together with mutation seen in 68% of cases. There was a significant association between CD274mutation/deletion and TNFRSF14mutation (p= 0.001). CD274 (PD-L1) and TNFRSF14 are ligands for the co-inhibitory receptor PD1 and BTLA on T-helper cells, respectively, their inactivation may free T-cell activities, promoting their help to malignant B-cells. In support of this, both the proportion of activated T-cells (CD4+CD69+/CD4+) within the proximity of malignant B-cells, and the level of transformed blasts were significantly higher in cases with CD274/TNFRSF14genetic abnormalities than those without these changes. Both CD274and TNFRSF14genetic changes were significantly associated with Hashimoto’s thyroiditis (p= 0.01, p= 0.04, respectively), and CD274mutation/deletion additionally associated with increased erythrocyte sedimentation rate (p= 0.0001). In conclusion, CD274/TNFRSF14inactivation in thyroid MALT lymphoma B-cells may deregulate their interaction with T-cells, promoting co-stimulations and impairing peripheral tolerance.

Published
2024
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63. Supplementary Figure from Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

Author

Vesely, Clare, primary, Wong, Yien Ning Sophia, primary, Childs, Alexa, primary, Akarca, Ayse U., primary, Dhami, Pawan, primary, Vaikkinen, Heli, primary, Conde, Lucia, primary, Herrero, Javier, primary, Ogunbiyi, Olagunju, primary, Gander, Amir, primary, Luong, Tu Vinh, primary, Thirlwell, Chrissie, primary, Caplin, Martyn, primary, Toumpanakis, Christos, primary, Peggs, Karl, primary, Quezada, Sergio A., primary, Marafioti, Teresa, primary, and Meyer, Tim, primary

Published
2023
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64. Supplementary Table from Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

Author

Vesely, Clare, primary, Wong, Yien Ning Sophia, primary, Childs, Alexa, primary, Akarca, Ayse U., primary, Dhami, Pawan, primary, Vaikkinen, Heli, primary, Conde, Lucia, primary, Herrero, Javier, primary, Ogunbiyi, Olagunju, primary, Gander, Amir, primary, Luong, Tu Vinh, primary, Thirlwell, Chrissie, primary, Caplin, Martyn, primary, Toumpanakis, Christos, primary, Peggs, Karl, primary, Quezada, Sergio A., primary, Marafioti, Teresa, primary, and Meyer, Tim, primary

Published
2023
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65. Supplementary Data from Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

Author

Vesely, Clare, primary, Wong, Yien Ning Sophia, primary, Childs, Alexa, primary, Akarca, Ayse U., primary, Dhami, Pawan, primary, Vaikkinen, Heli, primary, Conde, Lucia, primary, Herrero, Javier, primary, Ogunbiyi, Olagunju, primary, Gander, Amir, primary, Luong, Tu Vinh, primary, Thirlwell, Chrissie, primary, Caplin, Martyn, primary, Toumpanakis, Christos, primary, Peggs, Karl, primary, Quezada, Sergio A., primary, Marafioti, Teresa, primary, and Meyer, Tim, primary

Published
2023
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66. Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma

Author

Zhang, Hanyun, primary, AbdulJabbar, Khalid, additional, Moore, David A., additional, Akarca, Ayse, additional, Enfield, Katey S.S., additional, Jamal-Hanjani, Mariam, additional, Raza, Shan E. Ahmed, additional, Veeriah, Selvaraju, additional, Salgado, Roberto, additional, McGranahan, Nicholas, additional, Le Quesne, John, additional, Swanton, Charles, additional, Marafioti, Teresa, additional, and Yuan, Yinyin, additional

Published
2023
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67. Self-Supervised Deep Learning for Highly Efficient Spatial Immunophenotyping

Author

Zhang, Hanyun, primary, AbdulJabbar, Khalid, additional, Grunewald, Tami, additional, Akarca, Ayse, additional, Hagos, Yeman, additional, Sobhani, Faranak, additional, Lecat, Catherine, additional, Patel, Dominic, additional, Lee, Lydia, additional, Rodriguez-Justo, Manuel, additional, Yong, Kwee, additional, Ledermann, Jonathan A., additional, Le Quesne, John, additional, Hwang, E. Shelley, additional, Marafioti, Teresa, additional, and Yuan, Yinyin, additional

Published
2023
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68. Targeting the T cell receptor [beta]-chain constant region for immunotherapy of T cell malignancies

Author

Maciocia, Paul M, Wawrzyniecka, Patrycja A, Philip, Brian, Ricciardelli, Ida, Akarca, Ayse U, Onuoha, Shimobi C, Legut, Mateusz, Cole, David K, Sewell, Andrew K, Gritti, Giuseppe, Somja, Joan, Piris, Miguel A, Peggs, Karl S, Linch, David C, Marafioti, Teresa, and Pule, Martin A

Subjects
T cells -- Receptors, Antigen receptors, T cell -- Physiological aspects -- Genetic aspects -- Research, Non-Hodgkin's lymphomas -- Genetic aspects -- Care and treatment -- Research, Immunotherapy -- Research, Biological sciences, Health
Abstract

Mature T cell cancers are typically aggressive, treatment resistant and associated with poor prognosis. Clinical application of immunotherapeutic approaches has been limited by a lack of target antigens that discriminate malignant from healthy (normal) T cells. Unlike B cell depletion, pan-T cell aplasia is prohibitively toxic. We report a new targeting strategy based on the mutually exclusive expression of T cell receptor [beta]-chain constant domains 1 and 2 (TRBC1 and TRBC2). We identify an antibody with unique TRBC1 specificity and use it to demonstrate that normal and virus-specific T cell populations contain both TRBC1[sup.+] and TRBC2[sup.+] compartments, whereas malignancies are restricted to only one. As proof of concept for anti-TRBC immunotherapy, we developed anti-TRBC1 chimeric antigen receptor (CAR) T cells, which recognized and killed normal and malignant TRBC1[sup.+], but not TRBC2[sup.+], T cells in vitro and in a disseminated mouse model of leukemia. Unlike nonselective approaches targeting the entire T cell population, TRBC-targeted immunotherapy could eradicate a T cell malignancy while preserving sufficient normal T cells to maintain cellular immunity., Author(s): Paul M Maciocia [1]; Patrycja A Wawrzyniecka [1]; Brian Philip [1]; Ida Ricciardelli [2]; Ayse U Akarca [1]; Shimobi C Onuoha [3]; Mateusz Legut [4]; David K Cole [4]; [...]

Published
2017
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69. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

Abbosh, Christopher, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Le Quesne, John, Moore, David A., Veeriah, Selvaraju, Rosenthal, Rachel, Marafioti, Teresa, Kirkizlar, Eser, Watkins, Thomas B. K., McGranahan, Nicholas, Ward, Sophia, Martinson, Luke, Riley, Joan, Fraioli, Francesco, Al Bakir, Maise, Grnroos, Eva, Zambrana, Francisco, Endozo, Raymondo, Bi, Wenya Linda, Fennessy, Fiona M., Sponer, Nicole, Johnson, Diana, Laycock, Joanne, Shafi, Seema, Czyzewska-Khan, Justyna, Rowan, Andrew, Chambers, Tim, Matthews, Nik, Turajlic, Samra, Hiley, Crispin, Lee, Siow Ming, Forster, Martin D., Ahmad, Tanya, Falzon, Mary, Borg, Elaine, Lawrence, David, Hayward, Martin, Kolvekar, Shyam, Panagiotopoulos, Nikolaos, Janes, Sam M., Thakrar, Ricky, Ahmed, Asia, Blackhall, Fiona, Summers, Yvonne, Hafez, Dina, Naik, Ashwini, Ganguly, Apratim, Kareht, Stephanie, Shah, Rajesh, Joseph, Leena, Marie Quinn, Anne, Crosbie, Phil A., Naidu, Babu, Middleton, Gary, Langman, Gerald, Trotter, Simon, Nicolson, Marianne, Remmen, Hardy, Kerr, Keith, Chetty, Mahendran, Gomersall, Lesley, Fennell, Dean A., Nakas, Apostolos, Rathinam, Sridhar, Anand, Girija, Khan, Sajid, Russell, Peter, Ezhil, Veni, Ismail, Babikir, Irvin-Sellers, Melanie, Prakash, Vineet, Lester, Jason F., Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Oukrif, Dahmane, Akarca, Ayse U., Hartley, John A., Lowe, Helen L., Lock, Sara, Iles, Natasha, Bell, Harriet, Ngai, Yenting, Elgar, Greg, Szallasi, Zoltan, Schwarz, Roland F., Herrero, Javier, Stewart, Aengus, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Hackshaw, Allan, Shaw, Jacqui A., Zimmermann, Bernhard G., Swanton, Charles, Bosshard-Carter, Leticia, Goh, Gerald, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Horswell, Stuart, Bakir, Maise Al, Mitter, Richard, Escudero, Mickael, Xu, Hang, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Nye, Emma, Graca, Sofia, Joshi, Kroopa, Furness, Andrew, Ben Aissa, Assma, Wong, Yien Ning Sophia, Georgiou, Andy, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Taylor, Magali, Choudhary, Junaid, Califano, Raffaele, Taylor, Paul, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Moss, Stuart, Idries, Faiza, Bishop, Paul, Chaturvedi, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Rogan, Jane, Smith, Elaine, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Djearaman, Madava, Quesne, John Le, Thomas, Anne, Walter, Harriet, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Primrose, Lindsay, Amadi, Anita, Palmer, Shirley, Miller, Joy, Buchan, Keith, Edwards, Alison, Morgan, Fiona, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Dentro, Stefan, and Dessimoz, Christophe

Subjects
Lung cancer -- Genetic aspects -- Development and progression, DNA sequencing -- Methods, Phylogeny -- Observations, Cancer metastasis -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies., Author(s): Christopher Abbosh [1]; Nicolai J. Birkbak [1, 2]; Gareth A. Wilson [1, 2]; Mariam Jamal-Hanjani [1]; Tudor Constantin [3]; Raheleh Salari [3]; John Le Quesne [4]; David A. Moore [...]

Published
2017
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70. Impact of Double Expression of MYC and BCL-2 on Outcomes in Primary CNS Lymphoma: A UK Multicentre Analysis

Author

Poynton, Edward, primary, Chernucha, Emily, additional, Day, James, additional, Prodger, Catherine, additional, Hopkins, David, additional, Rakesh, Pallav, additional, O'Neill, Tess, additional, Thakrar, Nisha, additional, Akarca, Ayse, additional, Pomplun, Sabine, additional, Marafioti, Teresa, additional, Calaminici, Maria, additional, Chaganti, Sridhar, additional, McKay, Pam, additional, Smith, Jeffery, additional, Eyre, Toby A., additional, Martinez-Calle, Nicolas, additional, Cwynarski, Kate, additional, Fox, Christopher P., additional, and Okosun, Jessica, additional

Published
2022
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72. Dynamic Changes in the NK-, Neutrophil-, and B-cell Immunophenotypes Relevant in High Metastatic Risk Post Neoadjuvant Chemotherapy–Resistant Early Breast Cancers

Author

Gazinska, Patrycja, primary, Milton, Charlotte, additional, Iacovacci, Jacopo, additional, Ward, Joseph, additional, Buus, Richard, additional, Alaguthurai, Thanussuyah, additional, Graham, Rosalind, additional, Akarca, Ayse, additional, Lips, Esther, additional, Naidoo, Kalnisha, additional, Wesseling, Jelle, additional, Marafioti, Teresa, additional, Cheang, Maggie, additional, Gillett, Cheryl, additional, Wu, Yin, additional, Khan, Aadil, additional, Melcher, Alan, additional, Salgado, Roberto, additional, Dowsett, Mitch, additional, Tutt, Andrew, additional, Roxanis, Ioannis, additional, Haider, Syed, additional, and Irshad, Sheeba, additional

Published
2022
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73. Abstract 3096: Multi-region patient-derived xenograft models from non-small cell lung cancer patients enrolled in lung TRACERx

Author

Hynds, Robert E., primary, Pearce, David R., additional, Akarca, Ayse U., additional, Ward, Sophia, additional, Huebner, Ariana, additional, Pich, Oriol, additional, Wilson, Gareth A., additional, Gowers, Kate H., additional, Towns, Rebecca, additional, Aissa, Assma Ben, additional, Veeriah, Selvaraju, additional, Quezada, Sergio A., additional, Jamal-Hanjani, Mariam, additional, Janes, Sam M., additional, McGranahan, Nicholas, additional, Moore, David A., additional, Marafioti, Teresa, additional, and Swanton, Charles, additional

Published
2022
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74. High inter‐follicular spatial co‐localization of CD8+FOXP3+ with CD4+CD8+ cells predicts favorable outcome in follicular lymphoma

Author

Hagos, Yeman B., primary, Akarca, Ayse U., additional, Ramsay, Alan, additional, Rossi, Riccardo L., additional, Pomplun, Sabine, additional, Ngai, Victoria, additional, Moioli, Alessia, additional, Gianatti, Andrea, additional, Mcnamara, Christopher, additional, Rambaldi, Alessandro, additional, Quezada, Sergio A., additional, Linch, David, additional, Gritti, Giuseppe, additional, Yuan, Yinyin, additional, and Marafioti, Teresa, additional

Published
2022
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75. Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors

Author

Vesely, Clare, primary, Wong, Yien Ning Sophia, additional, Childs, Alexa, additional, Akarca, Ayse U., additional, Dhami, Pawan, additional, Vaikkinen, Heli, additional, Conde, Lucia, additional, Herrero, Javier, additional, Ogunbiyi, Olagunju, additional, Gander, Amir, additional, Luong, Tu Vinh, additional, Thirlwell, Chrissie, additional, Caplin, Martyn, additional, Toumpanakis, Christos, additional, Peggs, Karl, additional, Quezada, Sergio A., additional, Marafioti, Teresa, additional, and Meyer, Tim, additional

Published
2022
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76. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

Author

Au, Lewis, Hatipoglu, Emine, Robert De Massy, Marc, Litchfield, Kevin, Beattie, Gordon, Rowan, Andrew, Schnidrig, Desiree, Thompson, Rachael, Byrne, Fiona, Horswell, Stuart, Fotiadis, Nicos, Hazell, Steve, Nicol, David, Shepherd, Scott TC, Fendler, Annika, Mason, Robert, Del Rosario, Lyra, Edmonds, Kim, Lingard, Karla, Sarker, Sarah, Mangwende, Mary, Carlyle, Eleanor, Attig, Jan, Joshi, Kroopa, Uddin, Imran, Becker, Pablo D, Sunderland, Mariana Werner, Akarca, Ayse, Puccio, Ignazio, Yang, William W, Lund, Tom, Dhillon, Kim, Vasquez, Marcos Duran, Ghorani, Ehsan, Xu, Hang, Spencer, Charlotte, López, José I, Green, Anna, Mahadeva, Ula, Borg, Elaine, Mitchison, Miriam, Moore, David A, Proctor, Ian, Falzon, Mary, Pickering, Lisa, Furness, Andrew JS, Reading, James L, Salgado, Roberto, Marafioti, Teresa, Jamal-Hanjani, Mariam, PEACE Consortium, Kassiotis, George, Chain, Benny, Larkin, James, Swanton, Charles, Quezada, Sergio A, Turajlic, Samra, TRACERx Renal Consortium, and Apollo - University of Cambridge Repository

Subjects
multiregion, Receptors, Antigen, T-Cell, clear cell renal cell carcinoma, CD8-Positive T-Lymphocytes, autopsy, Clinical Trials, Phase II as Topic, Exome Sequencing, Tumor Microenvironment, Humans, TCR clonal replacement, Prospective Studies, TCR clonal maintenance, Carcinoma, Renal Cell, Immune Checkpoint Inhibitors, nivolumab, Sequence Analysis, RNA, Gene Expression Profiling, Endogenous Retroviruses, Genomics, Kidney Neoplasms, human endogenous retrovirus, Drug Resistance, Neoplasm, anti-PD-1, Tumor Escape, T cell receptor, Single-Cell Analysis
Abstract

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action.

Published
2021

77. TUMOR IMMUNOLOGY: Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

Author

McGranahan, Nicholas, Furness, Andrew J.S., Rosenthal, Rachel, Ramskov, Sofie, Lyngaa, Rikke, Saini, Sunil Kumar, Jamal-Hanjani, Mariam, Wilson, Gareth A., Birkbak, Nicolai J., Hiley, Crispin T., Watkins, Thomas B.K., Shafi, Seema, Murugaesu, Nirupa, Mitter, Richard, Akarca, Ayse U., Linares, Joseph, Marafioti, Teresa, Henry, Jake Y., Van Allen, Eliezer M., Miao, Diana, Schilling, Bastian, Schadendorf, Dirk, Garraway, Levi A., Makarov, Vladimir, Rizvi, Naiyer A., Snyder, Alexandra, Hellmann, Matthew D., Merghoub, Taha, Wolchok, Jedd D., Shukla, Sachet A., Wu, Catherine J., Peggs, Karl S., Chan, Timothy A., Hadrup, Sine R., Quezada, Sergio A., and Swanton, Charles

Published
2016
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78. Cover Image

Author

Granai, Massimo, primary, Lazzi, Stefano, additional, Mancini, Virginia, additional, Akarca, Ayse, additional, Santi, Raffaella, additional, Vergoni, Federica, additional, Sorrentino, Ester, additional, Guazzo, Raffaella, additional, Mundo, Lucia, additional, Cevenini, Gabriele, additional, Tripodo, Claudio, additional, Di Stefano, Gioia, additional, Puccini, Benedetta, additional, Ponzoni, Maurilio, additional, Sabattini, Elena, additional, Agostinelli, Claudio, additional, Bassüllü, Nuray, additional, Tecimer, Tülay, additional, Demiroz, Ahu Senem, additional, Mnango, Leah, additional, Dirnhofer, Stephan, additional, Quintanilla‐Martinez, Leticia, additional, Marafioti, Teresa, additional, Fend, Falko, additional, and Leoncini, Lorenzo, additional

Published
2021
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79. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

Author

Au, Lewis, primary, Hatipoglu, Emine, additional, Robert de Massy, Marc, additional, Litchfield, Kevin, additional, Beattie, Gordon, additional, Rowan, Andrew, additional, Schnidrig, Desiree, additional, Thompson, Rachael, additional, Byrne, Fiona, additional, Horswell, Stuart, additional, Fotiadis, Nicos, additional, Hazell, Steve, additional, Nicol, David, additional, Shepherd, Scott T.C., additional, Fendler, Annika, additional, Mason, Robert, additional, Del Rosario, Lyra, additional, Edmonds, Kim, additional, Lingard, Karla, additional, Sarker, Sarah, additional, Mangwende, Mary, additional, Carlyle, Eleanor, additional, Attig, Jan, additional, Joshi, Kroopa, additional, Uddin, Imran, additional, Becker, Pablo D., additional, Sunderland, Mariana Werner, additional, Akarca, Ayse, additional, Puccio, Ignazio, additional, Yang, William W., additional, Lund, Tom, additional, Dhillon, Kim, additional, Vasquez, Marcos Duran, additional, Ghorani, Ehsan, additional, Xu, Hang, additional, Spencer, Charlotte, additional, López, José I., additional, Green, Anna, additional, Mahadeva, Ula, additional, Borg, Elaine, additional, Mitchison, Miriam, additional, Moore, David A., additional, Proctor, Ian, additional, Falzon, Mary, additional, Pickering, Lisa, additional, Furness, Andrew J.S., additional, Reading, James L., additional, Salgado, Roberto, additional, Marafioti, Teresa, additional, Jamal-Hanjani, Mariam, additional, Kassiotis, George, additional, Chain, Benny, additional, Larkin, James, additional, Swanton, Charles, additional, Quezada, Sergio A., additional, Turajlic, Samra, additional, Abbosh, Chris, additional, Shiu, Kai-Keen, additional, Bridgewater, John, additional, Hochhauser, Daniel, additional, Forster, Martin, additional, Lee, Siow-Ming, additional, Ahmad, Tanya, additional, Papadatos-Pastos, Dionysis, additional, Janes, Sam, additional, Van Loo, Peter, additional, Enfield, Katey, additional, McGranahan, Nicholas, additional, Huebner, Ariana, additional, Beck, Stephan, additional, Parker, Peter, additional, Walczak, Henning, additional, Enver, Tariq, additional, Hynds, Rob, additional, Sinclair, Ron, additional, Lok, Chi-wah, additional, Rhodes, Zoe, additional, Moore, David, additional, Khiroya, Reena, additional, Trevisan, Giorgia, additional, Ellery, Peter, additional, Linch, Mark, additional, Brandner, Sebastian, additional, Hiley, Crispin, additional, Veeriah, Selvaraju, additional, Razaq, Maryam, additional, Shaw, Heather, additional, Attard, Gert, additional, Akther, Mita Afroza, additional, Naceur-Lombardelli, Cristina, additional, Manzano, Lizi, additional, Al-Bakir, Maise, additional, Summan, Simranpreet, additional, Kanu, Nnenna, additional, Ward, Sophie, additional, Asghar, Uzma, additional, Lim, Emilia, additional, Gishen, Faye, additional, Tookman, Adrian, additional, Stone, Paddy, additional, Stirling, Caroline, additional, Hunter, Nikki, additional, Vaughan, Sarah, additional, Spain, Lavinia, additional, Yan, Haixi, additional, Shum, Ben, additional, Yousaf, Nadia, additional, Popat, Sanjay, additional, Curtis, Olivia, additional, Stamp, Gordon, additional, Toncheva, Antonia, additional, Nye, Emma, additional, Murra, Aida, additional, Korteweg, Justine, additional, Josephs, Debra, additional, Chandra, Ashish, additional, Spicer, James, additional, Stewart, Ruby, additional, Iredale, Lara-Rose, additional, Mackay, Tina, additional, Deakin, Ben, additional, Enting, Debra, additional, Rudman, Sarah, additional, Ghosh, Sharmistha, additional, Karapagniotou, Lena, additional, Pintus, Elias, additional, Tutt, Andrew, additional, Howlett, Sarah, additional, Michalarea, Vasiliki, additional, Brenton, James, additional, Caldas, Carlos, additional, Fitzgerald, Rebecca, additional, Jimenez-Linan, Merche, additional, Provenzano, Elena, additional, Cluroe, Alison, additional, Stewart, Grant, additional, Watts, Colin, additional, Gilbertson, Richard, additional, McDermott, Ultan, additional, Tavare, Simon, additional, Beddowes, Emma, additional, Roxburgh, Patricia, additional, Biankin, Andrew, additional, Chalmers, Anthony, additional, Fraser, Sioban, additional, Oien, Karin, additional, Kidd, Andrew, additional, Blyth, Kevin, additional, Krebs, Matt, additional, Blackhall, Fiona, additional, Summers, Yvonne, additional, Dive, Caroline, additional, Marais, Richard, additional, Gomes, Fabio, additional, Carter, Mat, additional, Dransfield, Jo, additional, Le Quesne, John, additional, Fennell, Dean, additional, Shaw, Jacqui, additional, Naidu, Babu, additional, Baijal, Shobhit, additional, Tanchel, Bruce, additional, Langman, Gerald, additional, Robinson, Andrew, additional, Collard, Martin, additional, Cockcroft, Peter, additional, Ferris, Charlotte, additional, Bancroft, Hollie, additional, Kerr, Amy, additional, Middleton, Gary, additional, Webb, Joanne, additional, Kadiri, Salma, additional, Colloby, Peter, additional, Olisemeke, Bernard, additional, Wilson, Rodelaine, additional, Tomlinson, Ian, additional, Jogai, Sanjay, additional, Ottensmeier, Christian, additional, Harrison, David, additional, Loda, Massimo, additional, Flanagan, Adrienne, additional, McKenzie, Mairead, additional, Hackshaw, Allan, additional, Ledermann, Jonathan, additional, Chan, Kitty, additional, Sharp, Abby, additional, Farrelly, Laura, additional, Bridger, Hayley, additional, Challacombe, Ben, additional, Chowdhury, Simon, additional, Drake, William, additional, Fernando, Archana, additional, Harrison-Phipps, Karen, additional, Hill, Peter, additional, Horsfield, Catherine, additional, O'Brien, Tim, additional, Olsburgh, Jonathon, additional, Polson, Alexander, additional, Varia, Mary, additional, and Verma, Hema, additional

Published
2021
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80. Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

Abbosh, Christopher, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Le Quesne, John, Moore, David A., Veeriah, Selvaraju, Rosenthal, Rachel, Marafioti, Teresa, Kirkizlar, Eser, Watkins, Thomas B. K., McGranahan, Nicholas, Ward, Sophia, Martinson, Luke, Riley, Joan, Fraioli, Francesco, Al Bakir, Maise, Grnroos, Eva, Zambrana, Francisco, Endozo, Raymondo, Bi, Wenya Linda, Fennessy, Fiona M., Sponer, Nicole, Johnson, Diana, Laycock, Joanne, Shafi, Seema, Czyzewska-Khan, Justyna, Rowan, Andrew, Chambers, Tim, Matthews, Nik, Turajlic, Samra, Hiley, Crispin, Lee, Siow Ming, Forster, Martin D., Ahmad, Tanya, Falzon, Mary, Borg, Elaine, Lawrence, David, Hayward, Martin, Kolvekar, Shyam, Panagiotopoulos, Nikolaos, Janes, Sam M., Thakrar, Ricky, Ahmed, Asia, Blackhall, Fiona, Summers, Yvonne, Hafez, Dina, Naik, Ashwini, Ganguly, Apratim, Kareht, Stephanie, Shah, Rajesh, Joseph, Leena, Quinn, Anne Marie, Crosbie, Phil A., Naidu, Babu, Middleton, Gary, Langman, Gerald, Trotter, Simon, Nicolson, Marianne, Remmen, Hardy, Kerr, Keith, Chetty, Mahendran, Gomersall, Lesley, Fennell, Dean A., Nakas, Apostolos, Rathinam, Sridhar, Anand, Girija, Khan, Sajid, Russell, Peter, Ezhil, Veni, Ismail, Babikir, Irvin-Sellers, Melanie, Prakash, Vineet, Lester, Jason F., Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Oukrif, Dahmane, Akarca, Ayse U., Hartley, John A., Lowe, Helen L., Lock, Sara, Iles, Natasha, Bell, Harriet, Ngai, Yenting, Elgar, Greg, Szallasi, Zoltan, Schwarz, Roland F., Herrero, Javier, Stewart, Aengus, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Hackshaw, Allan, Shaw, Jacqui A., Zimmermann, Bernhard G., and Swanton, Charles

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Christopher Abbosh; Nicolai J. Birkbak; Gareth A. Wilson; Mariam Jamal-Hanjani; Tudor Constantin; Raheleh Salari; John Le Quesne; David A. Moore; Selvaraju Veeriah; Rachel Rosenthal; Teresa Marafioti; Eser Kirkizlar; Thomas [...]

Published
2018
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82. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.

Author

Pinato, David J., primary, Murray, Sam M, additional, Forner, Alejandro, additional, Kaneko, Takahiro, additional, Fessas, Petros, additional, Toniutto, Pierluigi, additional, Mínguez, Beatriz, additional, Cacciato, Valentina, additional, Avellini, Claudio, additional, Diaz, Alba, additional, Boyton, Rosemary J., additional, Altmann, Daniel M., additional, Goldin, Robert D, additional, Akarca, Ayse U, additional, Marafioti, Teresa, additional, Mauri, Francesco A, additional, Casagrande, Edoardo, additional, Grillo, Federica, additional, Giannini, Edoardo, additional, Bhoori, Sherrie, additional, and Mazzaferro, Vincenzo, additional

Published
2021
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83. Burkitt lymphoma with a granulomatous reaction: an M1/Th1‐polarised microenvironment is associated with controlled growth and spontaneous regression

Author

Granai, Massimo, primary, Lazzi, Stefano, additional, Mancini, Virginia, additional, Akarca, Ayse, additional, Santi, Raffaella, additional, Vergoni, Federica, additional, Sorrentino, Ester, additional, Guazzo, Raffaella, additional, Mundo, Lucia, additional, Cevenini, Gabriele, additional, Tripodo, Claudio, additional, Di Stefano, Gioia, additional, Puccini, Benedetta, additional, Ponzoni, Maurilio, additional, Sabattini, Elena, additional, Agostinelli, Claudio, additional, Bassüllü, Nuray, additional, Tecimer, Tülay, additional, Demiroz, Ahu Senem, additional, Mnango, Leah, additional, Dirnhofer, Stephan, additional, Quintanilla‐Martinez, Leticia, additional, Marafioti, Teresa, additional, Fend, Falko, additional, and Leoncini, Lorenzo, additional

Published
2021
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84. Abstract LB004: Nivolumab (NIVO) and ipilimumab (IPI) treatment in prostate cancer with an immunogenic signature: cohort 1 of the NEPTUNES multi-centre, two-stage biomarker-selected Phase II trial

Author

Linch, Mark D., primary, Wong, Yien Ning Sophia, additional, Jones, Robert, additional, Sankey, Peter, additional, Josephs, Debra H., additional, Crabb, Simon J., additional, Staffurth, John, additional, Zarkar, Anjali, additional, White, Laura, additional, Duggan, Marian, additional, Pellizzari, Giulia, additional, Wheeler, Graham, additional, Beare, Sandy, additional, Cartwright, Hayley, additional, Linares, Josep, additional, Akarca, Ayse, additional, Quezada, Sergio A., additional, Ensell, Leah, additional, Hartley, John, additional, Attard, Gerhardt, additional, Burr, Joanna, additional, Jayaram, Anuradha, additional, Kularatne, Bihani, additional, Kayani, Mahaz, additional, Chung, Moon, additional, Pritchard, Colin C., additional, Freeman, Alex, additional, Haider, Aiman, additional, and Marafioti, Teresa, additional

Published
2021
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85. Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian Angelova, Mihaela Puttick, Clare and Zhai, Haoran Caswell, Deborah R. Lu, Wei-Ting Dietzen, Michelle Galanos, Panagiotis Evangelou, Konstantinos and Bellelli, Roberto Lim, Emilia L. Watkins, Thomas B. K. and Rowan, Andrew Teixeira, Vitor H. Zhao, Yue Chen, Haiquan and Ngo, Bryan Zalmas, Lykourgos-Panagiotis Al Bakir, Maise and Hobor, Sebastijan Gronroos, Eva Pennycuick, Adam Nigro, Ersilia Campbell, Brittany B. Brown, William L. Akarca, Ayse U. Marafioti, Teresa Wu, Mary Y. Howell, Michael and Boulton, Simon J. Bertoli, Cosetta Fenton, Tim R. de Bruin, Robertus A. M. Maya-Mendoza, Apolinar Santoni-Rugiu, Eric and Hynds, Robert E. Gorgoulis, Vassilis G. Jamal-Hanjani, Mariam and McGranahan, Nicholas Harris, Reuben S. Janes, Sam M. and Bartkova, Jirina Bakhoum, Samuel F. Bartek, Jiri Kanu, Nnennaya Swanton, Charles TRACERx Consortium

Subjects
viruses
Abstract

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast ductal carcinoma in situ, and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non-small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G(1) phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution. SIGNIFICANCE : This study reveals the dynamics and drivers of APOBEC3 gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution.

Published
2021

87. Induction of APOBEC3 exacerbates DNA replication stress and chromosomal instability in early breast and lung cancer evolution

Author

Vankatesan, Subramanian, Angelova, Mihaela, Puttick, Clare, Zhai, Haoran, Caswell, Deborah, Lu, Wei-Ting, Dietzen, Michelle, Galanos, Panagiotis, Evangelou, Konstantinos, Bellelli, Roberto, Lim, Emilia L, Watkins, Thomas B K, Rowan, Andrew, Teixeira, Vitor H, Zhao, Yue, Chen, Haiquan, Ngo, Bryan, Zalmas, Lykourgos-Panagiotis, Al Bakir, Maise, Hobor, Sebastijan, Gronroos, Eva, Pennycuick, Adam, Nigro, Ersilia, Campbell, Brittany B, Brown, William L, Akarca, Ayse U, Marafioti, Teresa, Wu, Mary Y, Howell, Michael, Boulton, Simon J, Bertoli, Cosetta, Fenton, Tim R., de Bruin, Robertus A M, Maya-Mendoza, Apolinar, Santoni-Rugiu, Eric, Hynds, Robert E, Gorgoulis, Vassilis G, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Harris, Reuben S, Janes, Sam M, Bartkova, Jirina, Bakhoum, Samuel F, Bartek, Jiri, Kanu, Nnennaya, Swanton, Charles, Vankatesan, Subramanian, Angelova, Mihaela, Puttick, Clare, Zhai, Haoran, Caswell, Deborah, Lu, Wei-Ting, Dietzen, Michelle, Galanos, Panagiotis, Evangelou, Konstantinos, Bellelli, Roberto, Lim, Emilia L, Watkins, Thomas B K, Rowan, Andrew, Teixeira, Vitor H, Zhao, Yue, Chen, Haiquan, Ngo, Bryan, Zalmas, Lykourgos-Panagiotis, Al Bakir, Maise, Hobor, Sebastijan, Gronroos, Eva, Pennycuick, Adam, Nigro, Ersilia, Campbell, Brittany B, Brown, William L, Akarca, Ayse U, Marafioti, Teresa, Wu, Mary Y, Howell, Michael, Boulton, Simon J, Bertoli, Cosetta, Fenton, Tim R., de Bruin, Robertus A M, Maya-Mendoza, Apolinar, Santoni-Rugiu, Eric, Hynds, Robert E, Gorgoulis, Vassilis G, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Harris, Reuben S, Janes, Sam M, Bartkova, Jirina, Bakhoum, Samuel F, Bartek, Jiri, Kanu, Nnennaya, and Swanton, Charles

Abstract

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast DCIS, and in pre-invasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx pre-invasive to invasive NSCLC lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models, revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in pre-invasive disease, providing fuel for selection early in cancer evolution.

Published
2021

88. Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, Angelova, Mihaela, Puttick, Clare, Zhai, Haoran, Caswell, Deborah R., Lu, Wei-ting, Dietzen, Michelle, Galanos, Panagiotis, Evangelou, Konstantinos, Bellelli, Roberto, Lim, Emilia L., Watkins, Thomas B.k., Rowan, Andrew, Teixeira, Vitor H., Zhao, Yue, Chen, Haiquan, Ngo, Bryan, Zalmas, Lykourgos-panagiotis, Al Bakir, Maise, Hobor, Sebastijan, Grönroos, Eva, Pennycuick, Adam, Nigro, Ersilia, Campbell, Brittany B., Brown, William L., Akarca, Ayse U., Marafioti, Teresa, Wu, Mary Y., Howell, Michael, Boulton, Simon J., Bertoli, Cosetta, Fenton, Tim R., De Bruin, Robertus A.m., Maya-mendoza, Apolinar, Santoni-rugiu, Eric, Hynds, Robert E., Gorgoulis, Vassilis G., Jamal-hanjani, Mariam, Mcgranahan, Nicholas, Harris, Reuben S., Janes, Sam M., Bartkova, Jirina, Bakhoum, Samuel F., Bartek, Jiri, Kanu, Nnennaya, Swanton, Charles, Venkatesan, Subramanian, Angelova, Mihaela, Puttick, Clare, Zhai, Haoran, Caswell, Deborah R., Lu, Wei-ting, Dietzen, Michelle, Galanos, Panagiotis, Evangelou, Konstantinos, Bellelli, Roberto, Lim, Emilia L., Watkins, Thomas B.k., Rowan, Andrew, Teixeira, Vitor H., Zhao, Yue, Chen, Haiquan, Ngo, Bryan, Zalmas, Lykourgos-panagiotis, Al Bakir, Maise, Hobor, Sebastijan, Grönroos, Eva, Pennycuick, Adam, Nigro, Ersilia, Campbell, Brittany B., Brown, William L., Akarca, Ayse U., Marafioti, Teresa, Wu, Mary Y., Howell, Michael, Boulton, Simon J., Bertoli, Cosetta, Fenton, Tim R., De Bruin, Robertus A.m., Maya-mendoza, Apolinar, Santoni-rugiu, Eric, Hynds, Robert E., Gorgoulis, Vassilis G., Jamal-hanjani, Mariam, Mcgranahan, Nicholas, Harris, Reuben S., Janes, Sam M., Bartkova, Jirina, Bakhoum, Samuel F., Bartek, Jiri, Kanu, Nnennaya, and Swanton, Charles

Abstract

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast ductal carcinoma in situ, and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non–small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution. Significance: This study reveals the dynamics and drivers of APOBEC3 gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution

Published
2021

89. Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease

Author

Pollara, Gabriele, primary, Turner, Carolin T., additional, Rosenheim, Joshua, additional, Chandran, Aneesh, additional, Bell, Lucy C. K., additional, Khan, Ayesha, additional, Patel, Amit, additional, Peralta, Luis Felipe, additional, Folino, Anna, additional, Akarca, Ayse, additional, Venturini, Cristina, additional, Baker, Tina, additional, Ecker, Simone, additional, Ricciardolo, Fabio L. M., additional, Marafioti, Teresa, additional, Ugarte-Gil, Cesar, additional, Moore, David A. J., additional, Chain, Benjamin M., additional, Tomlinson, Gillian S., additional, and Noursadeghi, Mahdad, additional

Published
2021
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90. Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, additional, Puttick, Clare, additional, Zhai, Haoran, additional, Caswell, Deborah R., additional, Lu, Wei-Ting, additional, Dietzen, Michelle, additional, Galanos, Panagiotis, additional, Evangelou, Konstantinos, additional, Bellelli, Roberto, additional, Lim, Emilia L., additional, Watkins, Thomas B.K., additional, Rowan, Andrew, additional, Teixeira, Vitor H., additional, Zhao, Yue, additional, Chen, Haiquan, additional, Ngo, Bryan, additional, Zalmas, Lykourgos-Panagiotis, additional, Al Bakir, Maise, additional, Hobor, Sebastijan, additional, Grönroos, Eva, additional, Pennycuick, Adam, additional, Nigro, Ersilia, additional, Campbell, Brittany B., additional, Brown, William L., additional, Akarca, Ayse U., additional, Marafioti, Teresa, additional, Wu, Mary Y., additional, Howell, Michael, additional, Boulton, Simon J., additional, Bertoli, Cosetta, additional, Fenton, Tim R., additional, de Bruin, Robertus A.M., additional, Maya-Mendoza, Apolinar, additional, Santoni-Rugiu, Eric, additional, Hynds, Robert E., additional, Gorgoulis, Vassilis G., additional, Jamal-Hanjani, Mariam, additional, McGranahan, Nicholas, additional, Harris, Reuben S., additional, Janes, Sam M., additional, Bartkova, Jirina, additional, Bakhoum, Samuel F., additional, Bartek, Jiri, additional, Kanu, Nnennaya, additional, and Swanton, Charles, additional

Published
2021
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91. Phenotypic Characteristics of the Tumour Microenvironment in Primary and Secondary Hepatocellular Carcinoma

Author

Fessas, Petros, primary, Spina, Paolo, additional, Boldorini, Renzo L., additional, Pirisi, Mario, additional, Minisini, Rosalba, additional, Mauri, Francesco A., additional, Simpson, Fraser, additional, Olivieri, Paola, additional, Gennari, Alessandra, additional, Wong, Ching Ngar, additional, Siddique, Abdul, additional, Goldin, Robert D., additional, Akarca, Ayse U., additional, Marafioti, Teresa, additional, and Pinato, David J., additional

Published
2021
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92. The lifespan and kinetics of human dendritic cell subsets and their precursors in health and inflammation

Author

Lubin, Ruth, Patel, Amit A., Mackerodt, Jonas, Zhang, Yan, Gvili, Rotem, Mulder, Kevin, Dutertre, Charles-Antoine, Jalali, Parinaaz, Glanville, James R.W., Hazan, Idit, Sridharan, Nikhila, Rivkin, Gurion, Akarca, Ayse, Marafioti, Teresa, Gilroy, Derek W., Kandel, Leonid, Mildner, Alexander, Wilensky, Asaf, Asquith, Becca, Ginhoux, Florent, Macallan, Derek, and Yona, Simon

Abstract

Dendritic cells (DC) are specialized mononuclear phagocytes that link innate and adaptive immunity. They comprise two principal subsets: plasmacytoid DC (pDC) and conventional DC (cDC). Understanding the generation, differentiation, and migration of cDC is critical for immune homeostasis. Through human in vivo deuterium-glucose labeling, we observed the rapid appearance of AXL+ Siglec6+ DC (ASDC) in the bloodstream. ASDC circulate for ∼2.16 days, while cDC1 and DC2 circulate for ∼1.32 and ∼2.20 days, respectively, upon release from the bone marrow. Interestingly, DC3, a cDC subset that shares several similarities with monocytes, exhibits a labeling profile closely resembling that of DC2. In a human in vivo model of cutaneous inflammation, ASDC were recruited to the inflammatory site, displaying a distinctive effector signature. Taken together, these results quantify the ephemeral circulating lifespan of human cDC and propose functions of cDC and their precursors that are rapidly recruited to sites of inflammation.

Published
2024
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93. Determinants of anti-PD1 response and resistance in clear cell renal cell carcinoma

Author

Au, Lewis, primary, Hatipoglu, Emine, additional, de Massy, Marc Robert, additional, Litchfield, Kevin, additional, Rowan, Andrew, additional, Thompson, Rachael, additional, Schnidrig, Desiree, additional, Byrne, Fiona, additional, Beattie, Gordon, additional, Horswell, Stuart, additional, Fotiadis, Nicos, additional, Hazell, Steve, additional, Nicol, David, additional, Shepherd, Scott Thomas Colville, additional, Fendler, Annika, additional, Mason, Robert, additional, Attig, Jan, additional, Joshi, Kroopa, additional, Uddin, Imran, additional, Becker, Pablo, additional, Sunderland, Mariana Werner, additional, Akarca, Ayse, additional, Puccio, Ignazio, additional, Yang, William, additional, Lund, Tom, additional, Dhillon, Kim, additional, Vasquez, Marcos Duran, additional, Ghorani, Ehsan, additional, Xu, Hang, additional, López, José Ignacio, additional, Green, Anna, additional, Mahadeva, Ula, additional, Borg, Elaine, additional, Mitchison, Miriam, additional, Moore, David, additional, Proctor, Ian, additional, Falzon, Mary, additional, Furness, Andrew, additional, Pickering, Lisa, additional, Reading, James L., additional, Salgado, Roberto, additional, Marafioti, Teresa, additional, Jamal-Hanjani, Mariam, additional, Kassiotis, George, additional, Chain, Benny, additional, Larkin, James, additional, Swanton, Charles, additional, Quezada, Sergio A, additional, and Turajlic, Samra, additional

Published
2021
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94. Transcriptional analysis of multiple ovarian cancer cohorts reveals prognostic and immunomodulatory consequences of ERV expression

Author

Natoli, Marina, primary, Gallon, John, additional, Lu, Haonan, additional, Amgheib, Ala, additional, Pinato, David J, additional, Mauri, Francesco A, additional, Marafioti, Teresa, additional, Akarca, Ayse U, additional, Ullmo, Ines, additional, Ip, Jacey, additional, Aboagye, Eric O, additional, Brown, Robert, additional, Karadimitris, Anastasios, additional, and Ghaem-Maghami, Sadaf, additional

Published
2021
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96. Antitumor activity without on-target off-tumor toxicity of GD2–chimeric antigen receptor T cells in patients with neuroblastoma

Author

Straathof, Karin, primary, Flutter, Barry, additional, Wallace, Rebecca, additional, Jain, Neha, additional, Loka, Thalia, additional, Depani, Sarita, additional, Wright, Gary, additional, Thomas, Simon, additional, Cheung, Gordon Weng-Kit, additional, Gileadi, Talia, additional, Stafford, Sian, additional, Kokalaki, Evangelia, additional, Barton, Jack, additional, Marriott, Clare, additional, Rampling, Dyanne, additional, Ogunbiyi, Olumide, additional, Akarca, Ayse U., additional, Marafioti, Teresa, additional, Inglott, Sarah, additional, Gilmour, Kimberly, additional, Al-Hajj, Muhammad, additional, Day, William, additional, McHugh, Kieran, additional, Biassoni, Lorenzo, additional, Sizer, Natalie, additional, Barton, Claire, additional, Edwards, David, additional, Dragoni, Ilaria, additional, Silvester, Julie, additional, Dyer, Karen, additional, Traub, Stephanie, additional, Elson, Lily, additional, Brook, Sue, additional, Westwood, Nigel, additional, Robson, Lesley, additional, Bedi, Ami, additional, Howe, Karen, additional, Barry, Ailish, additional, Duncan, Catriona, additional, Barone, Giuseppe, additional, Pule, Martin, additional, and Anderson, John, additional

Published
2020
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97. Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer

Author

Pennycuick, Adam, primary, Teixeira, Vitor H., additional, AbdulJabbar, Khalid, additional, Raza, Shan E. Ahmed, additional, Lund, Tom, additional, Akarca, Ayse U., additional, Rosenthal, Rachel, additional, Kalinke, Lukas, additional, Chandrasekharan, Deepak P., additional, Pipinikas, Christodoulos P., additional, Lee-Six, Henry, additional, Hynds, Robert E., additional, Gowers, Kate H.C., additional, Henry, Jake Y., additional, Millar, Fraser R., additional, Hagos, Yeman B., additional, Denais, Celine, additional, Falzon, Mary, additional, Moore, David A., additional, Antoniou, Sophia, additional, Durrenberger, Pascal F., additional, Furness, Andrew J., additional, Carroll, Bernadette, additional, Marceaux, Claire, additional, Asselin-Labat, Marie-Liesse, additional, Larson, William, additional, Betts, Courtney, additional, Coussens, Lisa M., additional, Thakrar, Ricky M., additional, George, Jeremy, additional, Swanton, Charles, additional, Thirlwell, Christina, additional, Campbell, Peter J., additional, Marafioti, Teresa, additional, Yuan, Yinyin, additional, Quezada, Sergio A., additional, McGranahan, Nicholas, additional, and Janes, Sam M., additional

Published
2020
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98. Megakaryocytes, erythropoietic and granulopoietic cells express CAL2 antibody in myeloproliferative neoplasms carrying CALR gene mutations

Author

Ali, Hebah, primary, Puccio, Ignazio, additional, Akarca, Ayse U., additional, Bob, Roshanak, additional, Pomplun, Sabine, additional, Keong Wong, Wai, additional, Gupta, Rajeev, additional, Sekhar, Mallika, additional, Lambert, Jonathan, additional, Al‐Masri, Hytham, additional, Stein, Harald, additional, and Marafioti, Teresa, additional

Published
2020
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99. Integrated phenotyping of the anti-cancer immune response in HIV-associated hepatocellular carcinoma

Author

Pinato, David J., primary, Kaneko, Takahiro, additional, Forner, Alejandro, additional, Minguez, Beatriz, additional, Giannini, Edoardo Giovanni, additional, Díaz, Alba, additional, Grillo, Federica, additional, Mauri, Francesco, additional, Pria, Alessia Dalla, additional, Goldin, Robert D., additional, Casagrande, Edoardo, additional, Cacciato, Valentina, additional, Akarca, Ayse, additional, Marafioti, Teresa, additional, Bhoori, Sherrie, additional, Bower, Mark, additional, Brau, Norbert, additional, and Mazzaferro, Vincenzo, additional

Published
2020
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100. Intratumoural (IT) evolutionary landscape of high-risk prostate cancer and outcome: The PROGENY (PROstate cancer GENomic heterogeneitY) study of genomic and immune parameters.

Author

Jayaram, Anuradha, primary, Goh, Gerald, additional, Kularatne, Bihani Yoshana, additional, Waterhouse, Jasmin, additional, Shanmugabavan, Yaalini, additional, Rowan, Andrew, additional, Wong, Yien Ning Sophia, additional, Freeman, Alex, additional, Akarca, Ayse, additional, Herrero, Javier, additional, Rosenthal, Rachel, additional, McGranahan, Nicholas, additional, Hung, Michelle, additional, Emberton, Mark, additional, Attard, Gerhardt, additional, Quezada, Sergio A., additional, Marafioti, Teresa, additional, Ahmed, Hashim Uddin, additional, Swanton, Charles, additional, and Linch, Mark David, additional

Published
2020
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