Cancer Immunotherapy and Biomarkers
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It is demonstrated that clinically available mRNA vaccines targeting non-tumour-related antigens are potent immune modulators capable of sensitizing tumours to ICIs and SARS-CoV-2 mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.
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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.
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@article{Claussen2025SARS,
title = {SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade},
author = {Catherine M. Claussen and Adam Grippin and Christiano Marconi and Sage Copling and Nan Li and Chen Braun and Cole Woody and Elliana Young and Priti Gupta and Min Wang and Annette Wu and Seong Dong Jeong and Dhruvkumar Soni and Frances Weidert and Chao Xie and Edward E. Goldenberg and Andrew Kim and Chong Zhao and Anna DeVries and Paul Castillo and Rishabh Lohray and Michael K. Rooney and Benjamin R. Schrank and Yifan Wang and Yifan Ma and En‐Ting Chang and Ramez Kouzy and Kyle Dyson and Jordan Jafarnia and Nina Nariman and Gregory W. Gladish and Jacob New and Ada Argueta and Diana Amaya and Nagheme Thomas and Andria Doty and Joe Chen and Nikhil Copling and Gabriel Alatrash and Julie M. Simon and Alicia Bea Davies and William Dennis and Richard Liang and Jeff Lewis and Wei Xiong and Waree Rinsurongkawong and Ara Vaporciyan and Andrew Johns and Ashley Aaroe and Soman Abraham and Lee Andrews and Kiran K. Badami and Janna A. Baganz and Pratibha Bajwa and Gregory Barbosa and Hannah C. Beird and K Brock and Elizabeth M. Burton and Juan P. Cata and Caroline Chung and John Crommett and Michael Cutherell and Bouthaina S. Dabaja and Hiba Dagher and Kevin M. Daniels and Mary Domask and Giulio Draetta and Paul Edelkamp and Sarah C. Fisher and Katy Elizabeth French and P. Andrew Futreal and Maria Gaeta and Myrna C. B. Godoy and Drew Goldstein and Jillian R. Gunther and Katherine A. Hutcheson and David A. Jaffray and Jeff Wang Jin and Teny Matthew John and Trey Kell and Mark Knafl and Rayson C. Kwan and J. Jack Lee and Jennifer K. Litton and Kevin W. McEnery and Mary Anne McGuire and Benjamin Mescher and Tejo Musunuru and Mayoora Muthu and Joseph Nates and Craig S. Owen and Priyadharshini Padmakumar and Nicholas Palaskas and Jay J. Patel and Sabitha Prabhakaran and L. Ramsey and Vinod Ravi and Cristhiam Rojas Hernandez and Bilja Sajith and Paul Scheet},
journal = {Nature},
year = {2025},
doi = {10.1038/s41586-025-09655-y},
url = {https://doi.org/10.1038/s41586-025-09655-y}
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