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

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; Chris Abbosh; Kai‐Keen Shiu; John Bridgewater; Daniel Hochhauser; Martin Förster; Siow Ming 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; George Kassiotis; Benny Chain; James Larkin; Charles Swanton; Sergio A. Quezada; Samra Turajlic; 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

doi:10.1016/j.ccell.2021.10.001

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

Lewis Au(Royal Marsden NHS Foundation Trust), Emine Hatipoglu(Royal Marsden NHS Foundation Trust), Marc Robert de Massy(Cancer Research UK), Kevin Litchfield(The Francis Crick Institute), Gordon Beattie(Cancer Research UK), Andrew Rowan(The Francis Crick Institute), Désirée Schnidrig(The Francis Crick Institute), R. Houston Thompson(The Francis Crick Institute), Fiona Byrne(The Francis Crick Institute), Stuart Horswell(The Francis Crick Institute), Nicos Fotiadis(Institute of Cancer Research), Steve Hazell(Royal Marsden NHS Foundation Trust), David Nicol(Royal Marsden NHS Foundation Trust), Scott T.C. Shepherd(Royal Marsden NHS Foundation Trust), Annika Fendler(The Francis Crick Institute), Robert M. Mason(Royal Marsden NHS Foundation Trust), Lyra Del Rosario(Royal Marsden NHS Foundation Trust), Kim Edmonds(Royal Marsden NHS Foundation Trust), Karla Lingard(Royal Marsden NHS Foundation Trust), Sarah Sarker(Royal Marsden NHS Foundation Trust), Mary Mangwende(Royal Marsden NHS Foundation Trust), Eleanor Carlyle(Royal Marsden NHS Foundation Trust), Jan Attig(The Francis Crick Institute), Kroopa Joshi(Cancer Research UK), Imran Uddin(Cancer Research UK), Pablo D. Becker(London Cancer), Mariana Werner Sunderland(London Cancer), Ayse U. Akarca(University College Hospital), Ignazio Puccio(University College Hospital), William Yang(University College Hospital), Tom Lund(Royal Marsden Hospital), Kim Dhillon(University College Hospital), Marcos Duran Vasquez(Cancer Research UK), Ehsan Ghorani(Cancer Research UK), Hang Xu(The Francis Crick Institute), Charlotte Spencer(The Francis Crick Institute), José I. López(BioCruces Health research Institute), Anna Green(St Thomas' Hospital), Ula Mahadeva(St Thomas' Hospital), Elaine Borg(University College Hospital), Miriam Mitchison(University College Hospital), David A. Moore(University College Hospital), Ian Proctor(University College Hospital), Mary Falzon(University College Hospital), Lisa Pickering(Royal Marsden NHS Foundation Trust), Andrew J.S. Furness(Royal Marsden NHS Foundation Trust), James L. Reading(Cancer Research UK), Roberto Salgado(Peter MacCallum Cancer Centre), Teresa Marafioti(University College Hospital), Mariam Jamal‐Hanjani(Royal London Hospital), Chris Abbosh(The Francis Crick Institute), Kai‐Keen Shiu(London Cancer), John Bridgewater(Royal Marsden NHS Foundation Trust), Daniel Hochhauser(The Francis Crick Institute), Martin Förster(Cancer Research UK), Siow Ming Lee(Royal Marsden NHS Foundation Trust), Tanya Ahmad, Dionysis Papadatos-Pastos, Sam M. Janes, Peter Van Loo, Katey S.S. Enfield, Nicholas McGranahan, Ariana Huebner, Stephan Beck, Peter J. Parker(Royal Marsden NHS Foundation Trust), Henning Walczak, Tariq Enver, Robert E. Hynds, Ron Sinclair(London Cancer), Chi-wah Lok(London Cancer), Zoe Rhodes, David A. Moore(CRUK Lung Cancer Centre of Excellence), Reena Khiroya, Giorgia Trevisan(Peter MacCallum Cancer Centre), Peter Ellery, Mark Linch, Sebastian Brandner, Crispin T. Hiley(University College Hospital), 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(Royal Marsden NHS Foundation Trust), Lavinia Spain, Haixi Yan, Benjamin Shum, Eleanor Carlyle(Royal Marsden NHS Foundation Trust), Nadia Yousaf(Royal Marsden NHS Foundation Trust), Sanjay Popat(Royal Marsden NHS Foundation Trust), Olivia Curtis, Gordon Stamp(University College Hospital), Antonia Toncheva(London Cancer), Emma Nye(Royal Marsden NHS Foundation Trust), Aida Murra, Justine Korteweg, Debra H. Josephs, Ashish Chandra(Cancer Research UK), James Spicer, Ruby M. Stewart, Lara-Rose Iredale, Tina Mackay, Ben Deakin, Debra Enting, Sarah Rudman(Royal Marsden NHS Foundation Trust), Sharmistha Ghosh, Lena Karapagniotou, Elias Pintus, Andrew Tutt(London Cancer), Sarah Howlett, Vasiliki Michalarea(Royal Marsden NHS Foundation Trust), James D. Brenton, Carlos Caldas, Rebecca C. Fitzgerald, Merche Jimenez-Linan(Royal Marsden NHS Foundation Trust), Elena Provenzano(Royal Marsden NHS Foundation Trust), Alison D. Cluroe, Grant D. Stewart(Royal Marsden NHS Foundation Trust), 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(Royal Marsden NHS Foundation Trust), Fiona Blackhall, Yvonne Summers, Caroline Dive, Richard Marais(Royal Marsden NHS Foundation Trust), Fábio Gomes(The Francis Crick Institute), Mat Carter, Jo Dransfield(The Francis Crick Institute), John Le Quesne, Dean A. Fennell, Jacqui Shaw, Babu Naidu, Shobhit Baijal, Bruce Tanchel(BioCruces Health research Institute), Gerald Langman, Andrew Robinson, Martin Collard, Peter Cockcroft, Charlotte Ferris, Hollie Bancroft, Amy Kerr, Gary Middleton(Royal Marsden NHS Foundation Trust), Joanne Webb, Salma Kadiri, Peter Colloby(The Francis Crick Institute), Bernard Olisemeke, Rodelaine Wilson, Ian Tomlinson, Sanjay Jogai, Christian H. Ottensmeier, David J. Harrison, Massimo Loda, Adrienne M. Flanagan, Mairead McKenzie(University College Hospital), Allan Hackshaw, Jonathan A. Ledermann, Kitty S. Chan(University College Hospital), Abby Sharp, Laura Farrelly, Hayley Bridger, George Kassiotis(The Francis Crick Institute), Benny Chain(University College London), James Larkin(Royal Marsden NHS Foundation Trust), Charles Swanton(CRUK Lung Cancer Centre of Excellence), Sergio A. Quezada(CRUK Lung Cancer Centre of Excellence), Samra Turajlic(The Francis Crick Institute), Ben Challacombe(London Cancer), Ashish Chandra, Simon Chowdhury, William Drake(University College Hospital), Archana Fernando, Karen Harrison‐Phipps, Steve Hazell(Royal Marsden NHS Foundation Trust), Peter Hill(University College Hospital), Catherine Horsfield, Tim O’Brien, Jonathon Olsburgh, Alexander Polson, Sarah Rudman(Royal Marsden NHS Foundation Trust), Mary Varia(University College Hospital), Hema Verma

Cancer Cell

October 28, 2021

10.1016/j.ccell.2021.10.001

Cited by 252Open Access

Full Text

Abstract

T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action.

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