- October 22, 2025
- Steven Lin, et al., MD Anderson
Topic/Product:
Inflammation Panel 250, Inflammation Panel AQ, Oncology
Disease Area:
Oncology
Sample Type:
Plasma
Abstract
Immune checkpoint inhibitors (ICIs) extend survival in many patients with cancer but are ineffective in patients without pre-existing immunity1,2,3,4,5,6,7,8,9. 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 processes10,11,12,13,14. 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.
Authors & Affiliations
Adam J. Grippin¹²⁹, Christiano Marconi²²⁹, Sage Copling³²⁹, Nan Li¹²⁹, Chen Braun¹, Cole Woody¹, Elliana Young⁴, Priti Gupta¹, Min Wang¹, Annette Wu¹, Seong Dong Jeong⁵⁶, Dhruvkumar Soni², Frances Weidert², Chao Xie², Eden Goldenberg², Andrew Kim³, Chong Zhao², Anna DeVries², Paul Castillo²⁷, Rishabh Lohray⁸, Michael K. Rooney¹, Benjamin R. Schrank¹, Yifan Wang¹, Yifan Ma¹, Enoch Chang¹, Ramez Kouzy¹, Kyle Dyson⁹, Jordan Jafarnia³, Nina Nariman³, Gregory Gladish¹⁰, Jacob New¹¹, Ada Argueta¹, Diana Amaya¹, Nagheme Thomas², Andria Doty², Joe Chen¹, Nikhil Copling¹², Gabriel Alatrash¹, Julie Simon¹³, Alicia Bea Davies¹³, William Dennis¹, Richard Liang¹, Jeff Lewis¹⁴, Xiong Wei¹⁴, Waree Rinsurongkawong¹⁴, Ara A. Vaporciyan¹⁵, Andrew Johns¹⁶, D3CODE Team¹⁷*, Jack Lee¹⁸, Ji-Hyun Lee¹⁹, Ryan Sun¹⁸, Padmanee Sharma¹⁶²⁰²¹, Hai Tran¹⁴, Jianjun Zhang¹⁴, Don L. Gibbons¹⁴, Jennifer Wargo¹³, Betty Y. S. Kim⁵⁶, John V. Heymach¹⁴, Hector R. Mendez-Gomez², Wen Jiang¹, Elias J. Sayour²⁷³⁰, & Steven H. Lin¹³⁰
¹ Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
² Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, University of Florida, Gainesville, FL, USA
³ McGovern Medical School, Houston, TX, USA
⁴ Department of Enterprise Data Engineering and Analytics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
⁵ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
⁶ Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
⁷ Department of Pediatrics, Division of Hematology-Oncology, University of Florida, Gainesville, FL, USA
⁸ Department of Dermatology, Baylor College of Medicine, Houston, TX, USA
⁹ Department of Pathology, Stanford University, Stanford, CA, USA
¹⁰ Department of Thoracic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
¹¹ Scripps Health, San Diego, CA, USA
¹² University of North Carolina, Chapel Hill, NC, USA
¹³ Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
¹⁴ Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
¹⁵ Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
¹⁶ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
¹⁷ The University of Texas MD Anderson Cancer Center, Houston, TX, USA
¹⁸ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
¹⁹ Department of Biostatistics, The University of Florida, Gainesville, FL, USA
²⁰ Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
²¹ James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
²⁹ These authors contributed equally to this work
³⁰ These authors jointly supervised this work