A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer
Yin Wu, Dhruva Biswas, Ieva Usaite, Mihaela Angelova, Stefan Boeing, Takahiro Karasaki, Selvaraju Veeriah, Justyna Czyzewska-Khan, Cienne Morton, Magdalene Joseph, Sonya Hessey, James L. Reading, Andrew Georgiou, Maise Al-Bakir, Nicolai J. Birkbak, Gillian Price, Mohammed S. Khalil, Keith M. Kerr, Shirley Richardson, Heather Cheyne, Tracey Cruickshank, Gareth A. Wilson, Rachel Rosenthal, Hugo J.W.L. Aerts, Madeleine Hewish, Girija Anand, Sajid Khan, Kelvin Lau, Michael Sheaff, Peter Schmid, Louise Lim, John Conibear, Roland F. Schwarz, Tom L. Kaufmann, Matthew R. Huska, Jacqui Shaw, Joan Riley, Lindsay Primrose, Dean A. Fennell, Allan Hackshaw, Yenting Ngai, Abigail Sharp, Oliver Pressey, Sean Smith, Nicole Gower, Harjot Kaur Dhanda, Kitty S. Chan, Sonal Chakraborty, Kevin Litchfield, Krupa Thakkar, Jonathan Tugwood, Alexandra Clipson, Caroline Dive, Dominic G. Rothwell, Alastair Kerr, Elaine Kilgour, Fiona J. E. Morgan, Malgorzata Kornaszewska, Richard Attanoos, Helen Davies, Katie Baker, Mathew Carter, Colin R. Lindsay, Fábio Gomes, Fiona Blackhall, Lynsey Priest, Matthew Krebs, Anshuman Chaturvedi, Pedro Oliveira, Zoltán Szállási, Gary Royle, Catarina Veiga, Marcin Skrzypski, Roberto Salgado, Miklós Dióssy, Alan Kirk, Mo Asif, John Butler, Rocco Bilancia, Nikos Kostoulas, Mathew Thomas, Mairead MacKenzie, Maggie Wilcox, Apostolos Nakas, Sridhar Rathinam, Rebecca Boyles, Mohamad Tufail, Amrita Bajaj, Keng Ang, Mohammed Fiyaz Chowdhry, Michael Shackcloth, Julius Asante-Siaw, Angela Leek, Nicola Totten, Jack Davies Hodgkinson, Peter Van Loo, William Monteiro, Hilary Marshal, Kevin G. Blyth, Craig Dick
Abstract
Abstract Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral Vδ1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8 + T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RA − CD27 − effector memory Vδ1 T cells in tumors and, most strikingly, with the numbers of CD103 + tissue-resident Vδ1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating Vδ1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer.