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1. Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models

Author

Hynds, Robert E., Huebner, Ariana, Pearce, David R., Hill, Mark S., Akarca, Ayse U., Moore, David A., Ward, Sophia, Gowers, Kate H. C., Karasaki, Takahiro, Al Bakir, Maise, Wilson, Gareth A., Pich, Oriol, Martínez-Ruiz, Carlos, Hossain, A. S. Md Mukarram, Pearce, Simon P., Sivakumar, Monica, Ben Aissa, Assma, Grönroos, Eva, Chandrasekharan, Deepak, Kolluri, Krishna K., Towns, Rebecca, Wang, Kaiwen, Cook, Daniel E., Bosshard-Carter, Leticia, Naceur-Lombardelli, Cristina, Rowan, Andrew J., Veeriah, Selvaraju, Litchfield, Kevin, Crosbie, Philip A. J., Dive, Caroline, Quezada, Sergio A., Janes, Sam M., Jamal-Hanjani, Mariam, Marafioti, Teresa, McGranahan, Nicholas, and Swanton, Charles

Published
2024
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4. ConCORDe-Net: Cell Count Regularized Convolutional Neural Network for Cell Detection in Multiplex Immunohistochemistry Images

Author

Hagos, Yeman Brhane, Narayanan, Priya Lakshmi, Akarca, Ayse U., Marafioti, Teresa, and Yuan, Yinyin

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

In digital pathology, cell detection and classification are often prerequisites to quantify cell abundance and explore tissue spatial heterogeneity. However, these tasks are particularly challenging for multiplex immunohistochemistry (mIHC) images due to high levels of variability in staining, expression intensity, and inherent noise as a result of preprocessing artefacts. We proposed a deep learning method to detect and classify cells in mIHC whole-tumour slide images of breast cancer. Inspired by inception-v3, we developed Cell COunt RegularizeD Convolutional neural Network (ConCORDe-Net) which integrates conventional dice overlap and a new cell count loss function for optimizing cell detection, followed by a multi-stage convolutional neural network for cell classification. In total, 20447 cells, belonging to five cell classes were annotated by experts from 175 patches extracted from 6 whole-tumour mIHC images. These patches were randomly split into training, validation and testing sets. Using ConCORDe-Net, we obtained a cell detection F1 score of 0.873, which is the best score compared to three state of the art methods. In particular, ConCORDe-Net excels at detecting closely located and weakly stained cells compared to other methods. Incorporating cell count loss in the objective function regularizes the network to learn weak gradient boundaries and separate weakly stained cells from background artefacts. Moreover, cell classification accuracy of 96.5% was achieved. These results support that incorporating problem-specific knowledge such as cell count into deep learning-based cell detection architectures improve the robustness of the algorithm., Comment: MICCAI2019 accepted, 3 figures,8.5 pages

Published
2019

5. Integrated phenotyping of the anti-cancer immune response in HIV-associated hepatocellular carcinoma

Author

Pinato, David J., Kaneko, Takahiro, D’Alessio, Antonio, Forner, Alejandro, Fessas, Petros, Minguez, Beatriz, Giannini, Edoardo G., Grillo, Federica, Díaz, Alba, Mauri, Francesco A., Fulgenzi, Claudia A.M., Dalla Pria, Alessia, Goldin, Robert D., Pieri, Giulia, Toniutto, Pierluigi, Avellini, Claudio, Plaz Torres, Maria Corina, Akarca, Ayse U., Marafioti, Teresa, Bhoori, Sherrie, Miró, Jose María, Bower, Mark, Bräu, Norbert, and Mazzaferro, Vincenzo

Published
2023
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6. Geospatial immune variability illuminates differential evolution of lung adenocarcinoma

Author

AbdulJabbar, Khalid, Raza, Shan E. Ahmed, Rosenthal, Rachel, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Akarca, Ayse, and Lund, Tom

Subjects
Immune system -- Genetic aspects -- Health aspects, Lung cancer, Non-small cell -- Development and progression -- Genetic aspects, Biological sciences, Health
Abstract

Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape.sup.1-5. However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort.sup.6. Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multisample cohort of 970 patients with lung adenocarcinoma, tumors with more than one immune cold region had a higher risk of relapse, independently of tumor size, stage and number of samples per patient. In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer-stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes. Multiregion spatial histology, exome and transcriptome data from patients with non-small cell lung cancer suggest that cancer subclones from immune cold regions diversify later than subclones from immune hot regions, Author(s): Khalid AbdulJabbar [sup.1] [sup.2] , Shan E. Ahmed Raza [sup.1] [sup.2] , Rachel Rosenthal [sup.3] [sup.4] , Mariam Jamal-Hanjani [sup.3] [sup.5] , Selvaraju Veeriah [sup.3] [sup.4] , Ayse Akarca [...]

Published
2020
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7. Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress

Author

Burt, Richard, Dey, Aditi, Aref, Sarah, Aguiar, Melanie, Akarca, Ayse, Bailey, Katharine, Day, William, Hooper, Steven, Kirkwood, Amy, Kirschner, Kristina, Lee, Soo-Wah, Lo Celso, Cristina, Manji, Jiten, Mansour, Marc R., Marafioti, Teresa, Mitchell, Rachel J., Muirhead, Robert C., Cheuk Yan Ng, Kenton, Pospori, Constandina, Puccio, Ignazio, Zuborne-Alapi, Krisztina, Sahai, Erik, and Fielding, Adele K.

Published
2019
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11. Impact of MYC and BCL2 double expression on outcomes in primary CNS lymphoma: a UK multicenter analysis

Author

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

Published
2024
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12. Correction to: Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program

Author

Granai, Massimo, Mundo, Lucia, Akarca, Ayse U., Siciliano, Maria Chiara, Rizvi, Hasan, Mancini, Virginia, Onyango, Noel, Nyagol, Joshua, Abinya, Nicholas Othieno, Maha, Ibrahim, Margielewska, Sandra, Wei, Wenbin, Bibas, Michele, Piccaluga, Pier Paolo, Quintanilla-Martinez, Leticia, Fend, Falko, Lazzi, Stefano, Leoncini, Lorenzo, and Marafioti, Teresa

Published
2020
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13. Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program

Author

Granai, Massimo, Mundo, Lucia, Akarca, Ayse U., Siciliano, Maria Chiara, Rizvi, Hasan, Mancini, Virginia, Onyango, Noel, Nyagol, Joshua, Abinya, Nicholas Othieno, Maha, Ibrahim, Margielewska, Sandra, Wei, Wenbin, Bibas, Michele, Piccaluga, Pier Paolo, Quintanilla-Martinez, Leticia, Fend, Falko, Lazzi, Stefano, Leoncini, Lorenzo, and Marafioti, Teresa

Published
2020
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14. CD47 expression in acute myeloid leukemia varies according to genotype

Author

Marra, Andrea, primary, Akarca, Ayse U, additional, Martino, Giovanni, additional, Ramsay, Alan, additional, Ascani, Stefano, additional, Perriello, Vincenzo Maria, additional, O’Nions, Jenny, additional, Wilson, Andrew J, additional, Gupta, Rajeev, additional, Childerhouse, Anna, additional, Proctor, Ian, additional, Rodriguez-Justo, Manuel, additional, Pomplun, Sabine, additional, Martelli, Maria Paola, additional, Lo Celso, Cristina, additional, Falini, Brunangelo, additional, and Marafioti, Teresa, additional

Published
2023
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15. Phenotyping of lymphoproliferative tumours generated in xenografts of non-small cell lung cancer

Author

Pearce, David R., primary, Akarca, Ayse U., additional, De Maeyer, Roel P. H., additional, Kostina, Emily, additional, Huebner, Ariana, additional, Sivakumar, Monica, additional, Karasaki, Takahiro, additional, Shah, Kavina, additional, Janes, Sam M., additional, McGranahan, Nicholas, additional, Reddy, Venkat, additional, Akbar, Arne N., additional, Moore, David A., additional, Marafioti, Teresa, additional, Swanton, Charles, additional, and Hynds, Robert E., additional

Published
2023
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16. 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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17. 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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18. 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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19. 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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21. 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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22. 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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23. 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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24. Correction to: Single‑cell profiling of myasthenia gravis identifies a pathogenic T cell signature

Author

Ingelfinger, Florian, Krishnarajah, Sinduya, Kramer, Michael, Utz, Sebastian G, Galli, Edoardo, Lutz, Mirjam, Zwicky, Pascale, Akarca, Ayse U, Jurado, Nicole Puertas, Ulutekin, Can, Bamert, David, Widmer, Corinne C, Piccoli, Luca, Sallusto, Federica, Núñez, Nicolás Gonzalo, Marafioti, Teresa, Schneiter, Didier, Opitz, Isabelle, Lanzavecchia, Antonio, Jung, Hans H, De Feo, Donatella, Mundt, Sarah, Schreiner, Bettina, Becher, Burkhard, University of Zurich, Schreiner, Bettina, and Becher, Burkhard

Subjects
2734 Pathology and Forensic Medicine, 2728 Neurology (clinical), 10255 Clinic for Thoracic Surgery, 10032 Clinic for Oncology and Hematology, 2804 Cellular and Molecular Neuroscience, 610 Medicine & health, 10040 Clinic for Neurology
Published
2021

25. 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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26. 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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27. 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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28. 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

30. 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

31. 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

32. Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature

Author

Ingelfinger, Florian, Krishnarajah, Sinduya, Kramer, Michael, Utz, Sebastian G, Galli, Edoardo, Lutz, Mirjam, Zwicky, Pascale, Akarca, Ayse U, Jurado, Nicole Puertas, Ulutekin, Can, Bamert, David, Widmer, Corinne C, Piccoli, Luca, Sallusto, Federica, Núñez, Nicolás Gonzalo; https://orcid.org/0000-0003-3837-270X, Marafioti, Teresa, Schneiter, Didier, Opitz, Isabelle, Lanzavecchia, Antonio, Jung, Hans H, De Feo, Donatella, Mundt, Sarah, Schreiner, Bettina, Becher, Burkhard; https://orcid.org/0000-0002-1541-7867, Ingelfinger, Florian, Krishnarajah, Sinduya, Kramer, Michael, Utz, Sebastian G, Galli, Edoardo, Lutz, Mirjam, Zwicky, Pascale, Akarca, Ayse U, Jurado, Nicole Puertas, Ulutekin, Can, Bamert, David, Widmer, Corinne C, Piccoli, Luca, Sallusto, Federica, Núñez, Nicolás Gonzalo; https://orcid.org/0000-0003-3837-270X, Marafioti, Teresa, Schneiter, Didier, Opitz, Isabelle, Lanzavecchia, Antonio, Jung, Hans H, De Feo, Donatella, Mundt, Sarah, Schreiner, Bettina, and Becher, Burkhard; https://orcid.org/0000-0002-1541-7867

Abstract

Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG. By creating a comprehensive immune map, we identified two dysregulated subsets of inflammatory circulating memory T helper (Th) cells. These signature ThCD103 and ThGM cells populated the diseased thymus, were reduced in the blood of MG patients, and were inversely correlated with disease severity. Both signature Th subsets rebounded in the blood of MG patients after surgical thymus removal, indicative of their role as cellular markers of disease activity. Together, this in-depth analysis of the immune landscape of MG provides valuable insight into disease pathogenesis, suggests novel biomarkers and identifies new potential therapeutic targets for treatment.

Published
2021

33. 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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34. 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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35. 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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36. 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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37. Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4+ T Cells

Author

Śledzińska, Anna, primary, Vila de Mucha, Maria, additional, Bergerhoff, Katharina, additional, Hotblack, Alastair, additional, Demane, Dafne Franz, additional, Ghorani, Ehsan, additional, Akarca, Ayse U., additional, Marzolini, Maria A.V., additional, Solomon, Isabelle, additional, Vargas, Frederick Arce, additional, Pule, Martin, additional, Ono, Masahiro, additional, Seddon, Benedict, additional, Kassiotis, George, additional, Ariyan, Charlotte E., additional, Korn, Thomas, additional, Marafioti, Teresa, additional, Lord, Graham M., additional, Stauss, Hans, additional, Jenner, Richard G., additional, Peggs, Karl S., additional, and Quezada, Sergio A., additional

Published
2020
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38. Immune microenvironment profiling of gastrointestinal stromal tumors (GIST) shows gene expression patterns associated to immune checkpoint inhibitors response

Author

Pantaleo, Maria A., primary, Tarantino, Giuseppe, additional, Agostinelli, Claudio, additional, Urbini, Milena, additional, Nannini, Margherita, additional, Saponara, Maristella, additional, Castelli, Chiara, additional, Stacchiotti, Silvia, additional, Fumagalli, Elena, additional, Gatto, Lidia, additional, Santini, Donatella, additional, De Leo, Antonio, additional, Marafioti, Teresa, additional, Akarca, Ayse, additional, Sabattini, Elena, additional, Pession, Andrea, additional, Ardizzoni, Andrea, additional, Indio, Valentina, additional, and Astolfi, Annalisa, additional

Published
2019
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40. Role of Epstein-Barr virus in transformation of follicular lymphoma to diffuse large B-cell lymphoma: a case report and review of the literature

Author

Granai, Massimo, primary, Ambrosio, Maria Raffaella, additional, Akarca, Ayse, additional, Mundo, Lucia, additional, Vergoni, Federica, additional, Santi, Raffaella, additional, Mancini, Virginia, additional, di Stefano, Gioia, additional, Amato, Teresa, additional, Bellan, Cristiana, additional, Puccini, Benedetta, additional, Sorrentino, Ester, additional, Naresh, Kikkeri N., additional, Leoncini, Lorenzo, additional, Marafioti, Teresa, additional, and Lazzi, Stefano, additional

Published
2019
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41. Hypoxic adaptation of leukemic cells infiltrating the CNS affords a therapeutic strategy targeting VEGFA

Author

Kato, Itaru, Nishinaka, Yoko, Nakamura, Masahiro, Akarca, Ayse U., Niwa, Akira, Ozawa, Hiroki, Yoshida, Kenichi, Mori, Makiko, Wang, Dapeng, Morita, Makiko, Ueno, Hiroo, Shiozawa, Yusuke, Shiraishi, Yuichi, Miyano, Satoru, Gupta, Rajeev, Umeda, Katsutsugu, Watanabe, Kenichiro, Koh, Katsuyoshi, Adachi, Souichi, Heike, Toshio, Saito, Megumu K., Sanada, Masashi, Ogawa, Seishi, Marafioti, Teresa, Watanabe, Akira, Nakahata, Tatsutoshi, and Enver, Tariq

Published
2017
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42. Megakaryocytes, erythropoietic and granulopoietic cells express CAL2 antibody in myeloproliferative neoplasms carrying CALR gene mutations.

Author

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

Subjects
GENETIC mutation, MEGAKARYOCYTES, ACUTE myeloid leukemia, MYELODYSPLASTIC syndromes, TUMORS, FETAL hemoglobin
Abstract

Testing for the CALR mutation is included in the updated WHO criteria for essential thrombocythaemia (ET) and primary myelofibrosis (PMF). We report on the application of the CAL2 monoclonal antibody, raised against the mutated CALR gene to myeloid cases. The immunostain was used on 116 acute myeloid leukaemias (AML) and 66 myeloproliferative neoplasms (MPN) or myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN). None of AML cases was stained by the CAL2 antibody, while 20/66 MPNs and MDS/MPNs appeared positive. Fourteen of the latter cases were studied by molecular techniques, and all showed aberrations of the CALR gene. In addition, CAL2 positivity was found in some small‐sized elements besides megakaryocytes. By double staining, these elements corresponded to small megakaryocytes as well as both erythroid and myeloid precursors. This finding suggests possible occurrence of CALR gene abnormalities in a stem cell. [ABSTRACT FROM AUTHOR]

Published
2021
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43. Cytotoxic CD4+ Cells in Chronic Lymphocytic Leukaemia: An Extended Immunophenotypic Analysis Examining Their Association with Cytomegalovirus Serostatus and Similarities with Cytotoxic CD8+ Cells

Author

Marzolini, Maria A V, primary, Akarca, Ayse, additional, Teng, Karen, additional, Marafioti, Teresa, additional, Gohil, Satyen H, additional, Nathwani, Amit C, additional, Newell, Evan, additional, Quezada, Sergio A, additional, and Peggs, Karl S, additional

Published
2018
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44. Erratum: Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

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

Published
2017
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45. Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies

Author

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

Published
2017
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46. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

Author

McGranahan, Nicholas, Furness, Andrew J S, Rosenthal, Rachel, Andersen, Sofie Ramskov, Lyngaa, Rikke Birgitte, 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 Reker, Quezada, Sergio A, Swanton, Charles, McGranahan, Nicholas, Furness, Andrew J S, Rosenthal, Rachel, Andersen, Sofie Ramskov, Lyngaa, Rikke Birgitte, 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 Reker, Quezada, Sergio A, and Swanton, Charles

Abstract

As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+)tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non-small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy-induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens.

Published
2016

47. VEGFA- a New Therapeutic Target in CNS Leukemia

Author

Kato, Itaru, primary, Nishinaka-Arai, Yoko, additional, Nakamura, Masahiro, additional, Akarca, Ayse U., additional, Niwa, Akira, additional, Ozawa, Hiroki, additional, Yoshida, Kenichi, additional, Mori, Makiko, additional, Wang, Dapeng, additional, Ueno, Hiroo, additional, Shiozawa, Yusuke, additional, Shiraishi, Yuichi, additional, Miyano, Satoru, additional, Gupta, Rajeev, additional, Umeda, Katsutsugu, additional, Watanabe, Kenichiro, additional, Koh, Katsuyoshi, additional, Adachi, Souichi, additional, Heike, Toshio, additional, Saito, Megumu K, additional, Sanada, Masashi, additional, Ogawa, Seishi, additional, Marafioti, Teresa, additional, Watanabe, Akira, additional, Nakahata, Tatsutoshi, additional, and Enver, Tariq, additional

Published
2016
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49. ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer–Containing Antibody–Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

Author

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

Published
2016
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50. Mechanistic and Pharmacodynamic Studies of Adct-301, a Pyrrolobenzodiazepine (PBD) Dimer-Containing Antibody Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies

Author

Flynn, Michael J., primary, van Berkel, Patrick H., additional, Zammarchi, Francesca, additional, Tyrer, Peter C., additional, Akarca, Ayse U., additional, Janghra, Narinder, additional, Shende, Vishvesh, additional, Linares, Joseph, additional, Marafioti, Teresa, additional, Williams, David G., additional, Howard, Philip W., additional, and Hartley, John A., additional

Published
2015
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