SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade
Adam Grippin(The University of Texas MD Anderson Cancer Center), Christiano Marconi(Allen Institute for Brain Science), Sage Copling(Office of Multidisciplinary Activities), Nan Li(The University of Texas MD Anderson Cancer Center), Chen Braun(The University of Texas MD Anderson Cancer Center), Cole Woody(The University of Texas MD Anderson Cancer Center), Elliana Young(The University of Texas MD Anderson Cancer Center), Priti Gupta(The University of Texas MD Anderson Cancer Center), Min Wang(The University of Texas MD Anderson Cancer Center), Annette Wu(The University of Texas MD Anderson Cancer Center), Seong Dong Jeong(The University of Texas MD Anderson Cancer Center), Dhruvkumar Soni(Allen Institute for Brain Science), Frances Weidert(Allen Institute for Brain Science), Chao Xie(Allen Institute for Brain Science), Eden Goldenberg(Allen Institute for Brain Science), Andrew Kim(Office of Multidisciplinary Activities), Chong Zhao(Allen Institute for Brain Science), Anna DeVries(Allen Institute for Brain Science), Paul Castillo(Allen Institute for Brain Science), Rishabh Lohray(Baylor College of Medicine), Michael K. Rooney(The University of Texas MD Anderson Cancer Center), Benjamin R. Schrank(The University of Texas MD Anderson Cancer Center), Yifan Wang(The University of Texas MD Anderson Cancer Center), Yifan Ma(The University of Texas MD Anderson Cancer Center), Enoch Chang(The University of Texas MD Anderson Cancer Center), Ramez Kouzy(The University of Texas MD Anderson Cancer Center), Kyle Dyson(Stanford University), Jordan Jafarnia(Office of Multidisciplinary Activities), Nina Nariman(Office of Multidisciplinary Activities), Gregory W. Gladish(The University of Texas MD Anderson Cancer Center), Jacob New(Scripps Health), Ada Argueta(The University of Texas MD Anderson Cancer Center), Diana Amaya(The University of Texas MD Anderson Cancer Center), Nagheme Thomas(Allen Institute for Brain Science), Andria Doty(Allen Institute for Brain Science), Joe Chen(The University of Texas MD Anderson Cancer Center), Nikhil Copling(University of North Carolina at Chapel Hill), Gabriel Alatrash(The University of Texas MD Anderson Cancer Center), Julie M. Simon(The University of Texas MD Anderson Cancer Center), Alicia Bea Davies(The University of Texas MD Anderson Cancer Center), William Dennis(The University of Texas MD Anderson Cancer Center), Richard Liang(The University of Texas MD Anderson Cancer Center), Jeff Lewis(The University of Texas MD Anderson Cancer Center), Xiong Wei(The University of Texas MD Anderson Cancer Center), Waree Rinsurongkawong(The University of Texas MD Anderson Cancer Center), Ara A. Vaporciyan(The University of Texas MD Anderson Cancer Center), Andrew Johns(The University of Texas MD Anderson Cancer Center), D3CODE Team(The University of Texas MD Anderson Cancer Center), Ashley Aaroe(The University of Texas MD Anderson Cancer Center), Sanu Abraham(The University of Texas MD Anderson Cancer Center), Lee Andrews(The University of Texas MD Anderson Cancer Center), Kiran K. Badami(The University of Texas MD Anderson Cancer Center), Janna A. Baganz(The University of Texas MD Anderson Cancer Center), Pratibha Bajwa(The University of Texas MD Anderson Cancer Center), Gregory Barbosa(The University of Texas MD Anderson Cancer Center), Hannah C. Beird(The University of Texas MD Anderson Cancer Center), K Brock(The University of Texas MD Anderson Cancer Center), Elizabeth M. Burton(The University of Texas MD Anderson Cancer Center), Juan P. Cata(The University of Texas MD Anderson Cancer Center), Caroline Chung(The University of Texas MD Anderson Cancer Center), Catherine M. Claussen(The University of Texas MD Anderson Cancer Center), John Crommett(The University of Texas MD Anderson Cancer Center), Michael Cutherell(The University of Texas MD Anderson Cancer Center), Bouthaina S. Dabaja(The University of Texas MD Anderson Cancer Center), Hiba Dagher(The University of Texas MD Anderson Cancer Center), Kevin M. Daniels(The University of Texas MD Anderson Cancer Center), Mary Domask(The University of Texas MD Anderson Cancer Center), Giulio Draetta(The University of Texas MD Anderson Cancer Center), Paul Edelkamp(The University of Texas MD Anderson Cancer Center), Sarah C. Fisher(The University of Texas MD Anderson Cancer Center), Katy Elizabeth French(The University of Texas MD Anderson Cancer Center), P. Andrew Futreal(The University of Texas MD Anderson Cancer Center), Maria Gaeta(The University of Texas MD Anderson Cancer Center), Myrna C. B. Godoy(The University of Texas MD Anderson Cancer Center), Drew Goldstein(The University of Texas MD Anderson Cancer Center), Jillian R. Gunther(The University of Texas MD Anderson Cancer Center), Kate Hutcheson(The University of Texas MD Anderson Cancer Center), David A. Jaffray(The University of Texas MD Anderson Cancer Center), Jeff Wang Jin(The University of Texas MD Anderson Cancer Center), Teny Matthew John(The University of Texas MD Anderson Cancer Center), Trey Kell(The University of Texas MD Anderson Cancer Center), Mark Knafl(The University of Texas MD Anderson Cancer Center), Rayson C. Kwan(The University of Texas MD Anderson Cancer Center), J. Jack Lee(The University of Texas MD Anderson Cancer Center), Jennifer K. Litton(The University of Texas MD Anderson Cancer Center), Kevin W. McEnery(The University of Texas MD Anderson Cancer Center), Mary Anne McGuire(The University of Texas MD Anderson Cancer Center), Benjamin Mescher(The University of Texas MD Anderson Cancer Center), Tejo Musunuru(The University of Texas MD Anderson Cancer Center), Mayoora Muthu(The University of Texas MD Anderson Cancer Center), Joseph Nates(The University of Texas MD Anderson Cancer Center), Craig S. Owen(The University of Texas MD Anderson Cancer Center), Priyadharshini Padmakumar(The University of Texas MD Anderson Cancer Center), Nicholas Palaskas(The University of Texas MD Anderson Cancer Center), Jay J. Patel(The University of Texas MD Anderson Cancer Center), Sabitha Prabhakaran(The University of Texas MD Anderson Cancer Center), L. Ramsey(The University of Texas MD Anderson Cancer Center), Vinod Ravi(The University of Texas MD Anderson Cancer Center), Cristhiam Rojas Hernandez(The University of Texas MD Anderson Cancer Center), Bilja Sajith(The University of Texas MD Anderson Cancer Center), Paul Scheet(The University of Texas MD Anderson Cancer Center), Stephanie Schmidt(The University of Texas MD Anderson Cancer Center), Kenna Shaw(The University of Texas MD Anderson Cancer Center), Sanjay Shete(The University of Texas MD Anderson Cancer Center), Daniel P. Shoenthal(The University of Texas MD Anderson Cancer Center), Lessley J. Stoltenberg(The University of Texas MD Anderson Cancer Center), Hussein A. Tawbi(The University of Texas MD Anderson Cancer Center), Anastasia Turin(The University of Texas MD Anderson Cancer Center), Samir Unni(The University of Texas MD Anderson Cancer Center), Benju Vicknamparampil(The University of Texas MD Anderson Cancer Center), Max C. Weber(The University of Texas MD Anderson Cancer Center), John N. Weinstein(The University of Texas MD Anderson Cancer Center), Scott E. Woodman(The University of Texas MD Anderson Cancer Center), Mark Wozny(The University of Texas MD Anderson Cancer Center), Carol C. Wu(The University of Texas MD Anderson Cancer Center), Jia Wu(The University of Texas MD Anderson Cancer Center), James C. Yao(The University of Texas MD Anderson Cancer Center), Chingyi Young(The University of Texas MD Anderson Cancer Center), Emily I. Yu(The University of Texas MD Anderson Cancer Center), Steven Zatorski(Ascension), Thomas A. Aloia(Ascension), John Cuenca Trujillo(Oracle (United States)), Christopher H. Gibbons(Oracle (United States)), Anai N. Kothari(Sarah Cannon Research Institute), Ishwaria M. Subbiah(Sarah Cannon Research Institute), Phillip Thompson(The University of Texas MD Anderson Cancer Center), J. Jack Lee(The University of Texas MD Anderson Cancer Center), Ji‐Hyun Lee(The University of Texas MD Anderson Cancer Center), Ryan Sun(The University of Texas MD Anderson Cancer Center), Padmanee Sharma(The University of Texas MD Anderson Cancer Center), Hai T. Tran(The University of Texas MD Anderson Cancer Center), Jianjun Zhang(The University of Texas MD Anderson Cancer Center), Don L. Gibbons(The University of Texas MD Anderson Cancer Center), Jennifer A. Wargo(The University of Texas MD Anderson Cancer Center), Betty Y.S. Kim(The University of Texas MD Anderson Cancer Center), John V. Heymach(Allen Institute for Brain Science), Héctor R. Méndez‐Gómez(Allen Institute for Brain Science), Wen Jiang(Allen Institute for Brain Science), Elias Sayour(Allen Institute for Brain Science), Steven H. Lin(The University of Texas MD Anderson Cancer Center)
Cited by 71Open Access
Abstract
Immune checkpoint inhibitors (ICIs) extend survival in many patients with cancer but are ineffective in patients without pre-existing immunity1–9. Although personalized mRNA cancer vaccines sensitize tumours to ICIs by directing immune attacks against preselected antigens, personalized vaccines are limited by complex and time-intensive manufacturing processes10–14. Here we show that mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to ICIs. In preclinical models, SARS-CoV-2 mRNA vaccines led to a substantial increase in type I interferon, enabling innate immune cells to prime CD8+ T cells that target tumour-associated antigens. Concomitant ICI treatment is required for maximal efficacy in immunologically cold tumours, which respond by increasing PD-L1 expression. Similar correlates of vaccination response are found in humans, including increases in type I interferon, myeloid–lymphoid activation in healthy volunteers and PD-L1 expression on tumours. Moreover, receipt of SARS-CoV-2 mRNA vaccines within 100 days of initiating ICI is associated with significantly improved median and three-year overall survival in multiple large retrospective cohorts. This benefit is similar among patients with immunologically cold tumours. Together, these results demonstrate that clinically available mRNA vaccines targeting non-tumour-related antigens are potent immune modulators capable of sensitizing tumours to ICIs. mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.
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