Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma
Authors: Lewis Au, Emine Hatipoglu, Marc Robert de Massy, Kevin Litchfield, Gordon Beattie, Andrew Rowan, Desiree Schnidrig, Rachael Thompson, Fiona Byrne, Stuart Horswell, Nicos Fotiadis, Steve Hazell, David Nicol, Scott T.C. Shepherd, Annika Fendler, Robert 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 Akarca, Ignazio Puccio, William W. 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 Forster, Siow-Ming Lee, Tanya Ahmad, Dionysis Papadatos-Pastos, Sam Janes, Peter Van Loo, Katey Enfield, Nicholas McGranahan, Ariana Huebner, Stephan Beck, Peter Parker, Henning Walczak, Tariq Enver, Rob Hynds, Ron Sinclair, Chi-wah Lok, Zoe Rhodes, David Moore, Reena Khiroya, Giorgia Trevisan, Peter Ellery, Mark Linch, Sebastian Brandner, Crispin Hiley, Selvaraju Veeriah, Maryam Razaq, Heather Shaw, Gert Attard, Mita Afroza Akther, Cristina Naceur-Lombardelli, Lizi Manzano, Maise Al-Bakir, Simranpreet Summan, Nnenna Kanu, Sophie Ward, Uzma Asghar, Emilia Lim, Faye Gishen, Adrian Tookman, Paddy Stone, Caroline Stirling, Nikki Hunter, Sarah Vaughan, Mary Mangwende, Lavinia Spain, Haixi Yan, Ben Shum, Eleanor Carlyle, Nadia Yousaf, Sanjay Popat, Olivia Curtis, Gordon Stamp, Antonia Toncheva, Emma Nye, Aida Murra, Justine Korteweg, Debra Josephs, Ashish Chandra, James Spicer, Ruby 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 Brenton, Carlos Caldas, Rebecca Fitzgerald, Merche Jimenez-Linan, Elena Provenzano, Alison Cluroe, Grant Stewart, Colin Watts, Richard Gilbertson, Ultan McDermott, Simon Tavare, Emma Beddowes, Patricia Roxburgh, Andrew Biankin, Anthony Chalmers, Sioban Fraser, Karin Oien, Andrew Kidd, Kevin Blyth, Matt Krebs, Fiona Blackhall, Yvonne Summers, Caroline Dive, Richard Marais, Fabio Gomes, Mat Carter, Jo Dransfield, John Le Quesne, Dean 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 Ottensmeier, David Harrison, Massimo Loda, Adrienne Flanagan, Mairead McKenzie, Allan Hackshaw, Jonathan Ledermann, Kitty 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
Journal: Cancer Cell (2021)

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