Portal de Periódicos da CAPES

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

2021; Cell Press; Volume: 39; Issue: 11 Linguagem: Inglês

10.1016/j.ccell.2021.10.001

1878-3686

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

Pancreatic and Hepatic Oncology Research

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