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48 results on '"Lewis, Claire E."'

2. Targeting of a STING Agonist to Perivascular Macrophages in Prostate Tumors Delays Resistance to Androgen Deprivation Therapy

Author

Al-janabi, Haider, primary, Moyes, Katy, additional, Allen, Richard J, additional, Fisher, Matthew, additional, Crespo, Mateus, additional, Gurel, Bora, additional, Rescigno, Pasquale, additional, De Bono, Johann, additional, Nunns, Harry, additional, Bailey, Christopher, additional, Juncker-Jensen, Anna, additional, Muthana, Munitta, additional, Phillips, Wayne A, additional, Pearson, Helen, additional, Taplin, Mary-Ellen, additional, Brown, Janet E, additional, and Lewis, Claire E, additional

Published
2024
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3. Using a pan-cancer atlas to investigate tumour associated macrophages as regulators of immunotherapy response.

Author

Coulton, Alexander, Murai, Jun, Qian, Danwen, Thakkar, Krupa, Lewis, Claire E., and Litchfield, Kevin

Subjects
MACROPHAGES, T cells, IMMUNE checkpoint proteins, REFERENCE sources, TUMORS
Abstract

The paradigm for macrophage characterization has evolved from the simple M1/M2 dichotomy to a more complex model that encompasses the broad spectrum of macrophage phenotypic diversity, due to differences in ontogeny and/or local stimuli. We currently lack an in-depth pan-cancer single cell RNA-seq (scRNAseq) atlas of tumour-associated macrophages (TAMs) that fully captures this complexity. In addition, an increased understanding of macrophage diversity could help to explain the variable responses of cancer patients to immunotherapy. Our atlas includes well established macrophage subsets as well as a number of additional ones. We associate macrophage composition with tumour phenotype and show macrophage subsets can vary between primary and metastatic tumours growing in sites like the liver. We also examine macrophage-T cell functional cross talk and identify two subsets of TAMs associated with T cell activation. Analysis of TAM signatures in a large cohort of immune checkpoint inhibitor-treated patients (CPI1000 +) identify multiple TAM subsets associated with response, including the presence of a subset of TAMs that upregulate collagen-related genes. Finally, we demonstrate the utility of our data as a resource and reference atlas for mapping of novel macrophage datasets using projection. Overall, these advances represent an important step in both macrophage classification and overcoming resistance to immunotherapies in cancer. Single cell sequencing can be used to examine tumour associated macrophages (TAM) and comparison between studies has been a challenge. Here the authors show a comparison tool to compare and contrast TAMs from different human tumour types and how these cells associate with T cells exploring further macrophage heterogeneity. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Non-canonical HIF-1 stabilization contributes to intestinal tumorigenesis

Author

Rohwer, Nadine, Jumpertz, Sandra, Erdem, Merve, Egners, Antje, Warzecha, Klaudia T., Fragoulis, Athanassios, Kühl, Anja A., Kramann, Rafael, Neuss, Sabine, Rudolph, Ines, Endermann, Tobias, Zasada, Christin, Apostolova, Ivayla, Gerling, Marco, Kempa, Stefan, Hughes, Russell, Lewis, Claire E., Brenner, Winfried, Malinowski, Maciej B., Stockmann, Martin, Schomburg, Lutz, Faller, William, Sansom, Owen J., Tacke, Frank, Morkel, Markus, and Cramer, Thorsten

Published
2019
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5. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models

Author

Keklikoglou, Ioanna, Cianciaruso, Chiara, Güç, Esra, Squadrito, Mario Leonardo, Spring, Laura M., Tazzyman, Simon, Lambein, Lore, Poissonnier, Amanda, Ferraro, Gino B., Baer, Caroline, Cassará, Antonino, Guichard, Alan, Iruela-Arispe, M. Luisa, Lewis, Claire E., Coussens, Lisa M., Bardia, Aditya, Jain, Rakesh K., Pollard, Jeffrey W., and De Palma, Michele

Published
2019
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8. Supplementary Data from Macrophages Mediate the Antitumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors

Author

Kwan, Amy, primary, Winder, Natalie, primary, Atkinson, Emer, primary, Al-Janabi, Haider, primary, Allen, Richard J., primary, Hughes, Russell, primary, Moamin, Mohammed, primary, Louie, Rikah, primary, Evans, Dhanajay, primary, Hutchinson, Matthew, primary, Capper, Drew, primary, Cox, Katie, primary, Handley, Joshua, primary, Wilshaw, Adam, primary, Kim, Taewoo, primary, Tazzyman, Simon J., primary, Srivastava, Sanjay, primary, Ottewell, Penelope, primary, Vadakekolathu, Jayakumar, primary, Pockley, Graham, primary, Lewis, Claire E., primary, Brown, Janet E., primary, Danson, Sarah J., primary, Conner, Joe, primary, and Muthana, Munitta, primary

Published
2023
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9. Data from Macrophages Mediate the Antitumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors

Author

Kwan, Amy, primary, Winder, Natalie, primary, Atkinson, Emer, primary, Al-Janabi, Haider, primary, Allen, Richard J., primary, Hughes, Russell, primary, Moamin, Mohammed, primary, Louie, Rikah, primary, Evans, Dhanajay, primary, Hutchinson, Matthew, primary, Capper, Drew, primary, Cox, Katie, primary, Handley, Joshua, primary, Wilshaw, Adam, primary, Kim, Taewoo, primary, Tazzyman, Simon J., primary, Srivastava, Sanjay, primary, Ottewell, Penelope, primary, Vadakekolathu, Jayakumar, primary, Pockley, Graham, primary, Lewis, Claire E., primary, Brown, Janet E., primary, Danson, Sarah J., primary, Conner, Joe, primary, and Muthana, Munitta, primary

Published
2023
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12. Supplementary Figures S1-S7 from Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

Author

Hughes, Russell, primary, Qian, Bin-Zhi, primary, Rowan, Charlotte, primary, Muthana, Munitta, primary, Keklikoglou, Ioanna, primary, Olson, Oakley C., primary, Tazzyman, Simon, primary, Danson, Sarah, primary, Addison, Christina, primary, Clemons, Mark, primary, Gonzalez-Angulo, Ana Maria, primary, Joyce, Johanna A., primary, De Palma, Michele, primary, Pollard, Jeffrey W., primary, and Lewis, Claire E., primary

Published
2023
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18. Supplementary Table S1 from Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

Author

Hughes, Russell, primary, Qian, Bin-Zhi, primary, Rowan, Charlotte, primary, Muthana, Munitta, primary, Keklikoglou, Ioanna, primary, Olson, Oakley C., primary, Tazzyman, Simon, primary, Danson, Sarah, primary, Addison, Christina, primary, Clemons, Mark, primary, Gonzalez-Angulo, Ana Maria, primary, Joyce, Johanna A., primary, De Palma, Michele, primary, Pollard, Jeffrey W., primary, and Lewis, Claire E., primary

Published
2023
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20. Data from Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

Author

Hughes, Russell, primary, Qian, Bin-Zhi, primary, Rowan, Charlotte, primary, Muthana, Munitta, primary, Keklikoglou, Ioanna, primary, Olson, Oakley C., primary, Tazzyman, Simon, primary, Danson, Sarah, primary, Addison, Christina, primary, Clemons, Mark, primary, Gonzalez-Angulo, Ana Maria, primary, Joyce, Johanna A., primary, De Palma, Michele, primary, Pollard, Jeffrey W., primary, and Lewis, Claire E., primary

Published
2023
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22. Supplementary Figure 2 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Muthana, Munitta, primary, Giannoudis, Athina, primary, Scott, Simon D., primary, Fang, Hsin-Yu, primary, Coffelt, Seth B., primary, Morrow, Fiona J., primary, Murdoch, Craig, primary, Burton, Julian, primary, Cross, Neil, primary, Burke, Bernard, primary, Mistry, Roshna, primary, Hamdy, Freddie, primary, Brown, Nicola J., primary, Georgopoulos, Lindsay, primary, Hoskin, Peter, primary, Essand, Magnus, primary, Lewis, Claire E., primary, and Maitland, Norman J., primary

Published
2023
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26. Supplementary Figure 4 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Muthana, Munitta, primary, Giannoudis, Athina, primary, Scott, Simon D., primary, Fang, Hsin-Yu, primary, Coffelt, Seth B., primary, Morrow, Fiona J., primary, Murdoch, Craig, primary, Burton, Julian, primary, Cross, Neil, primary, Burke, Bernard, primary, Mistry, Roshna, primary, Hamdy, Freddie, primary, Brown, Nicola J., primary, Georgopoulos, Lindsay, primary, Hoskin, Peter, primary, Essand, Magnus, primary, Lewis, Claire E., primary, and Maitland, Norman J., primary

Published
2023
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28. Supplementary Figure Legends 1-5, Methods from Angiopoietin-2 Regulates Gene Expression in TIE2-Expressing Monocytes and Augments Their Inherent Proangiogenic Functions

Author

Coffelt, Seth B., primary, Tal, Andrea O., primary, Scholz, Alexander, primary, De Palma, Michele, primary, Patel, Sunil, primary, Urbich, Carmen, primary, Biswas, Subhra K., primary, Murdoch, Craig, primary, Plate, Karl H., primary, Reiss, Yvonne, primary, and Lewis, Claire E., primary

Published
2023
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30. Supplementary Figure 1 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Muthana, Munitta, primary, Giannoudis, Athina, primary, Scott, Simon D., primary, Fang, Hsin-Yu, primary, Coffelt, Seth B., primary, Morrow, Fiona J., primary, Murdoch, Craig, primary, Burton, Julian, primary, Cross, Neil, primary, Burke, Bernard, primary, Mistry, Roshna, primary, Hamdy, Freddie, primary, Brown, Nicola J., primary, Georgopoulos, Lindsay, primary, Hoskin, Peter, primary, Essand, Magnus, primary, Lewis, Claire E., primary, and Maitland, Norman J., primary

Published
2023
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33. Supplementary Figure 3 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Muthana, Munitta, primary, Giannoudis, Athina, primary, Scott, Simon D., primary, Fang, Hsin-Yu, primary, Coffelt, Seth B., primary, Morrow, Fiona J., primary, Murdoch, Craig, primary, Burton, Julian, primary, Cross, Neil, primary, Burke, Bernard, primary, Mistry, Roshna, primary, Hamdy, Freddie, primary, Brown, Nicola J., primary, Georgopoulos, Lindsay, primary, Hoskin, Peter, primary, Essand, Magnus, primary, Lewis, Claire E., primary, and Maitland, Norman J., primary

Published
2023
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34. Supplementary Figure 5 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Muthana, Munitta, primary, Giannoudis, Athina, primary, Scott, Simon D., primary, Fang, Hsin-Yu, primary, Coffelt, Seth B., primary, Morrow, Fiona J., primary, Murdoch, Craig, primary, Burton, Julian, primary, Cross, Neil, primary, Burke, Bernard, primary, Mistry, Roshna, primary, Hamdy, Freddie, primary, Brown, Nicola J., primary, Georgopoulos, Lindsay, primary, Hoskin, Peter, primary, Essand, Magnus, primary, Lewis, Claire E., primary, and Maitland, Norman J., primary

Published
2023
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35. Data from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Muthana, Munitta, primary, Giannoudis, Athina, primary, Scott, Simon D., primary, Fang, Hsin-Yu, primary, Coffelt, Seth B., primary, Morrow, Fiona J., primary, Murdoch, Craig, primary, Burton, Julian, primary, Cross, Neil, primary, Burke, Bernard, primary, Mistry, Roshna, primary, Hamdy, Freddie, primary, Brown, Nicola J., primary, Georgopoulos, Lindsay, primary, Hoskin, Peter, primary, Essand, Magnus, primary, Lewis, Claire E., primary, and Maitland, Norman J., primary

Published
2023
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36. Supplementary Figure Legends from Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

Author

Hughes, Russell, primary, Qian, Bin-Zhi, primary, Rowan, Charlotte, primary, Muthana, Munitta, primary, Keklikoglou, Ioanna, primary, Olson, Oakley C., primary, Tazzyman, Simon, primary, Danson, Sarah, primary, Addison, Christina, primary, Clemons, Mark, primary, Gonzalez-Angulo, Ana Maria, primary, Joyce, Johanna A., primary, De Palma, Michele, primary, Pollard, Jeffrey W., primary, and Lewis, Claire E., primary

Published
2023
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40. Macrophages Mediate the Antitumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors

Author

Kwan, Amy, primary, Winder, Natalie, additional, Atkinson, Emer, additional, Al-Janabi, Haider, additional, Allen, Richard J., additional, Hughes, Russell, additional, Moamin, Mohammed, additional, Louie, Rikah, additional, Evans, Dhanajay, additional, Hutchinson, Matthew, additional, Capper, Drew, additional, Cox, Katie, additional, Handley, Joshua, additional, Wilshaw, Adam, additional, Kim, Taewoo, additional, Tazzyman, Simon J., additional, Srivastava, Sanjay, additional, Ottewell, Penelope, additional, Vadakekolathu, Jayakumar, additional, Pockley, Graham, additional, Lewis, Claire E., additional, Brown, Janet E., additional, Danson, Sarah J., additional, Conner, Joe, additional, and Muthana, Munitta, additional

Published
2021
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41. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models

Author

Keklikoglou, Ioanna, primary, Cianciaruso, Chiara, additional, Güç, Esra, additional, Squadrito, Mario Leonardo, additional, Spring, Laura M., additional, Tazzyman, Simon, additional, Lambein, Lore, additional, Poissonnier, Amanda, additional, Ferraro, Gino B., additional, Baer, Caroline, additional, Cassará, Antonino, additional, Guichard, Alan, additional, Iruela-Arispe, M. Luisa, additional, Lewis, Claire E., additional, Coussens, Lisa M., additional, Bardia, Aditya, additional, Jain, Rakesh K., additional, Pollard, Jeffrey W., additional, and De Palma, Michele, additional

Published
2018
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43. Non-canonical HIF-1 stabilization is essential for intestinal tumorigenesis

Author

Rohwer, Nadine, primary, Jumpertz, Sandra, additional, Erdem, Merve, additional, Egners, Antje, additional, Warzecha, Klaudia T., additional, Fragoulis, Athanassios, additional, Kühl, Anja A., additional, Kramann, Rafael, additional, Neuss, Sabine, additional, Rudolph, Ines, additional, Endermann, Tobias, additional, Zasada, Christin, additional, Apostolova, Ivayla, additional, Gerling, Marco, additional, Kempa, Stefan, additional, Hughes, Russell, additional, Lewis, Claire E., additional, Brenner, Winfried, additional, Malinowski, Maciej B., additional, Stockmann, Martin, additional, Schomburg, Lutz, additional, Faller, William, additional, Sansom, Owen, additional, Tacke, Frank, additional, Morkel, Markus, additional, and Cramer, Thorsten, additional

Published
2018
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45. Classification of current anticancer immunotherapies

Author

UCL - SSS/DDUV - Institut de Duve, Galluzzi, Lorenzo, Vacchelli, Erika, Bravo-San Pedro, José-Manuel, Buqué, Aitziber, Senovilla, Laura, Baracco, Elisa Elena, Bloy, Norma, Castoldi, Francesca, Abastado, Jean-Pierre, Agostinis, Patrizia, Apte, Ron N, Aranda, Fernando, Ayyoub, Maha, Beckhove, Philipp, Blay, Jean-Yves, Bracci, Laura, Caignard, Anne, Castelli, Chiara, Cavallo, Federica, Celis, Estaban, Cerundolo, Vincenzo, Clayton, Aled, Colombo, Mario P, Coussens, Lisa, Dhodapkar, Madhav V, Eggermont, Alexander M, Fearon, Douglas T, Wolf H, Fridman, Fucikova, Jitka, Gabrilovitch, Dmitry I, Galon, Jérôme, Garg, Abhishek, Ghiringhelli, François, Giaccone, Giuseppe, Gilboa, Eli, Gnjatic, Sacha, Hoos, Axel, Hosmalin, Anne, Jäger, Dirk, Kalinski, Pawel, Kärre, Klas, Kepp, Oliver, Kiessling, Rolf, Kirkwood, John M, Klein, Eva, Knuth, Alexander, Lewis, Claire E, Libiau, Roland, Lotze, Michael T, Lugli, Enrico, Mach, Jean-Pierre, Mattei, Fabrizio, Mavillo, Domenico, Melero, Ignacio, Melief, Cornelis J, Mittendorf, Elizabeth A, Moretta, Lorenzo, Odunsi, Adekunke, Okada, Hideho, Palucka, Anna Karolina, Peter, Marcus E, Pienta, Kenneth J, Porgador, Angel, Prendergast, George C, Rabinovich, Gabriel A, Restifo, Nicholas P, Rizvi, Naiyer, Sautès-Fridman, Catherine, Schreiber, Hans, Seliger, Barbara, Hiroshi, Shiku, Silva-Santos, Bruno, Smyth, Mark J, Speiser, Daniel E, Spisek, Radek, Srivastava, Pramod K, Taimadge, James E, Tartour, Eric, Van Der Burg, Sjoerd H, Van den Eynde, Benoît, Vile, Richard, Wagner, Hermann, Weber, Jeffrey S, Whiteside, Theresa L, Wolchok, Jedd D, Zitvogel, Laurence, Zou, Weiping, Kroemer, Guido, UCL - SSS/DDUV - Institut de Duve, Galluzzi, Lorenzo, Vacchelli, Erika, Bravo-San Pedro, José-Manuel, Buqué, Aitziber, Senovilla, Laura, Baracco, Elisa Elena, Bloy, Norma, Castoldi, Francesca, Abastado, Jean-Pierre, Agostinis, Patrizia, Apte, Ron N, Aranda, Fernando, Ayyoub, Maha, Beckhove, Philipp, Blay, Jean-Yves, Bracci, Laura, Caignard, Anne, Castelli, Chiara, Cavallo, Federica, Celis, Estaban, Cerundolo, Vincenzo, Clayton, Aled, Colombo, Mario P, Coussens, Lisa, Dhodapkar, Madhav V, Eggermont, Alexander M, Fearon, Douglas T, Wolf H, Fridman, Fucikova, Jitka, Gabrilovitch, Dmitry I, Galon, Jérôme, Garg, Abhishek, Ghiringhelli, François, Giaccone, Giuseppe, Gilboa, Eli, Gnjatic, Sacha, Hoos, Axel, Hosmalin, Anne, Jäger, Dirk, Kalinski, Pawel, Kärre, Klas, Kepp, Oliver, Kiessling, Rolf, Kirkwood, John M, Klein, Eva, Knuth, Alexander, Lewis, Claire E, Libiau, Roland, Lotze, Michael T, Lugli, Enrico, Mach, Jean-Pierre, Mattei, Fabrizio, Mavillo, Domenico, Melero, Ignacio, Melief, Cornelis J, Mittendorf, Elizabeth A, Moretta, Lorenzo, Odunsi, Adekunke, Okada, Hideho, Palucka, Anna Karolina, Peter, Marcus E, Pienta, Kenneth J, Porgador, Angel, Prendergast, George C, Rabinovich, Gabriel A, Restifo, Nicholas P, Rizvi, Naiyer, Sautès-Fridman, Catherine, Schreiber, Hans, Seliger, Barbara, Hiroshi, Shiku, Silva-Santos, Bruno, Smyth, Mark J, Speiser, Daniel E, Spisek, Radek, Srivastava, Pramod K, Taimadge, James E, Tartour, Eric, Van Der Burg, Sjoerd H, Van den Eynde, Benoît, Vile, Richard, Wagner, Hermann, Weber, Jeffrey S, Whiteside, Theresa L, Wolchok, Jedd D, Zitvogel, Laurence, Zou, Weiping, and Kroemer, Guido

Abstract

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.

Published
2015

46. Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

Author

Hughes, Russell, primary, Qian, Bin-Zhi, additional, Rowan, Charlotte, additional, Muthana, Munitta, additional, Keklikoglou, Ioanna, additional, Olson, Oakley C., additional, Tazzyman, Simon, additional, Danson, Sarah, additional, Addison, Christina, additional, Clemons, Mark, additional, Gonzalez-Angulo, Ana Maria, additional, Joyce, Johanna A., additional, De Palma, Michele, additional, Pollard, Jeffrey W., additional, and Lewis, Claire E., additional

Published
2015
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47. Classification of current anticancer immunotherapies

Author

Galluzzi, Lorenzo, primary, Vacchelli, Erika, additional, Pedro, José-Manuel Bravo-San, additional, Buqué, Aitziber, additional, Senovilla, Laura, additional, Baracco, Elisa Elena, additional, Bloy, Norma, additional, Castoldi, Francesca, additional, Abastado, Jean-Pierre, additional, Agostinis, Patrizia, additional, Apte, Ron N., additional, Aranda, Fernando, additional, Ayyoub, Maha, additional, Beckhove, Philipp, additional, Blay, Jean-Yves, additional, Bracci, Laura, additional, Caignard, Anne, additional, Castelli, Chiara, additional, Cavallo, Federica, additional, Celis, Estaban, additional, Cerundolo, Vincenzo, additional, Clayton, Aled, additional, Colombo, Mario P., additional, Coussens, Lisa, additional, Dhodapkar, Madhav V., additional, Eggermont, Alexander M., additional, Fearon, Douglas T., additional, Fridman, Wolf H., additional, Fučíková, Jitka, additional, Gabrilovich, Dmitry I., additional, Galon, Jérôme, additional, Garg, Abhishek, additional, Ghiringhelli, François, additional, Giaccone, Giuseppe, additional, Gilboa, Eli, additional, Gnjatic, Sacha, additional, Hoos, Axel, additional, Hosmalin, Anne, additional, Jäger, Dirk, additional, Kalinski, Pawel, additional, Kärre, Klas, additional, Kepp, Oliver, additional, Kiessling, Rolf, additional, Kirkwood, John M., additional, Klein, Eva, additional, Knuth, Alexander, additional, Lewis, Claire E., additional, Liblau, Roland, additional, Lotze, Michael T., additional, Lugli, Enrico, additional, Mach, Jean-Pierre, additional, Mattei, Fabrizio, additional, Mavilio, Domenico, additional, Melero, Ignacio, additional, Melief, Cornelis J., additional, Mittendorf, Elizabeth A., additional, Moretta, Lorenzo, additional, Odunsi, Adekunke, additional, Okada, Hideho, additional, Palucka, Anna Karolina, additional, Peter, Marcus E., additional, Pienta, Kenneth J., additional, Porgador, Angel, additional, Prendergast, George C., additional, Rabinovich, Gabriel A., additional, Restifo, Nicholas P., additional, Rizvi, Naiyer, additional, Sautès-Fridman, Catherine, additional, Schreiber, Hans, additional, Seliger, Barbara, additional, Shiku, Hiroshi, additional, Silva-Santos, Bruno, additional, Smyth, Mark J., additional, Speiser, Daniel E., additional, Spisek, Radek, additional, Srivastava, Pramod K., additional, Talmadge, James E., additional, Tartour, Eric, additional, Van Der Burg, Sjoerd H., additional, Van Den Eynde, Benoît J., additional, Vile, Richard, additional, Wagner, Hermann, additional, Weber, Jeffrey S., additional, Whiteside, Theresa L., additional, Wolchok, Jedd D., additional, Zitvogel, Laurence, additional, Zou, Weiping, additional, and Kroemer, Guido, additional

Published
2014
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48. Targeting a STING agonist to perivascular macrophages in prostate tumors delays resistance to androgen deprivation therapy.

Author

Al-Janabi H, Moyes K, Allen R, Fisher M, Crespo M, Gurel B, Rescigno P, de Bono J, Nunns H, Bailey C, Junker-Jensen A, Muthana M, Phillips WA, Pearson HB, Taplin ME, Brown JE, and Lewis CE

Subjects
Male, Animals, Mice, Humans, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant pathology, Androgen Antagonists therapeutic use, Androgen Antagonists pharmacology, Tumor-Associated Macrophages metabolism, Tumor-Associated Macrophages drug effects, Tumor-Associated Macrophages immunology, Prostatic Neoplasms drug therapy, Prostatic Neoplasms pathology, Drug Resistance, Neoplasm, Membrane Proteins metabolism, Membrane Proteins agonists, Macrophages metabolism, Macrophages immunology, Macrophages drug effects
Abstract

Background: Androgen deprivation therapy (ADT) is a front-line treatment for prostate cancer. In some men, their tumors can become refractory leading to the development of castration-resistant prostate cancer (CRPC). This causes tumors to regrow and metastasize, despite ongoing treatment, and impacts negatively on patient survival. ADT is known to stimulate the accumulation of immunosuppressive cells like protumoral tumor-associated macrophages (TAMs), myeloid-derived suppressor cells and regulatory T cells in prostate tumors, as well as hypofunctional T cells. Protumoral TAMs have been shown to accumulate around tumor blood vessels during chemotherapy and radiotherapy in other forms of cancer, where they drive tumor relapse. Our aim was to see whether such perivascular (PV) TAMs also accumulate in ADT-treated prostate tumors prior to CRPC, and, if so, whether selectively inducing them to express a potent immunostimulant, interferon beta (IFNβ), would stimulate antitumor immunity and delay CRPC., Methods: We used multiplex immunofluorescence to assess the effects of ADT on the distribution and activation status of TAMs, CD8+T cells, CD4+T cells and NK cells in mouse and/or human prostate tumors. We then used antibody-coated, lipid nanoparticles (LNPs) to selectively target a STING agonist, 2'3'-cGAMP (cGAMP), to PV TAMs in mouse prostate tumors during ADT., Results: TAMs accumulated at high density around blood vessels in response to ADT and expressed markers of a protumoral phenotype including folate receptor-beta (FR-β), MRC1 (CD206), CD169 and VISTA. Additionally, higher numbers of inactive (PD-1-) CD8+T cells and reduced numbers of active (CD69+) NK cells were present in these PV tumor areas. LNPs coated with an antibody to FR-β selectively delivered cGAMP to PV TAMs in ADT-treated tumors, where they activated STING and upregulated the expression of IFNβ. This resulted in a marked increase in the density of active CD8+T cells (along with CD4+T cells and NK cells) in PV tumor areas, and significantly delayed the onset of CRPC. Antibody depletion of CD8+T cells during LNP administration demonstrated the essential role of these cells in delay in CRPC induced by LNPs., Conclusion: Together, our data indicate that targeting a STING agonist to PV TAMs could be used to extend the treatment window for ADT in prostate cancer., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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