SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade

Grippin, AJ; Marconi, C; Copling, S; Li, N; Braun, C; Woody, C; Young, E; Gupta, P; Wang, M; Wu, A; Jeong, SD; Soni, D; Weidert, F; Xie, C; Goldenberg, E; Kim, A; Zhao, C; DeVries, A; Castillo, P; Lohray, R; Rooney, MK; Schrank, BR; Wang, Y; Ma, Y; Chang, E; Kouzy, R; Dyson, K; Jafarnia, J; Nariman, N; Gladish, G; New, J; Argueta, A; Amaya, D; Thomas, N; Doty, A; Chen, J; Copling, N; Alatrash, G; Simon, J; Davies, AB; Dennis, W; Liang, R; Lewis, J; Wei, X; Rinsurongkawong, W; Vaporciyan, AA; Johns, A; D3CODE Team; Lee, J; Lee, JH; Sun, R; Sharma, P; Tran, H; Zhang, J; Gibbons, DL; Wargo, J; Kim, BYS; Heymach, JV; Mendez-Gomez, HR; Jiang, W; Sayour, EJ; Lin, SH

Author(s): Grippin, AJ; Marconi, C; Copling, S; Li, N; Braun, C; Woody, C; Young, E; Gupta, P; Wang, M; Wu, A; Jeong, SD; Soni, D; Weidert, F; Xie, C; Goldenberg, E; Kim, A; Zhao, C; DeVries, A; Castillo, P; Lohray, R; Rooney, MK; Schrank, BR; Wang, Y; Ma, Y; Chang, E; Kouzy, R; Dyson, K; Jafarnia, J; Nariman, N; Gladish, G; New, J; Argueta, A; Amaya, D; Thomas, N; Doty, A; Chen, J; Copling, N; Alatrash, G; Simon, J; Davies, AB; Dennis, W; Liang, R; Lewis, J; Wei, X; Rinsurongkawong, W; Vaporciyan, AA; Johns, A; D3CODE Team; Lee, J; Lee, JH; Sun, R; Sharma, P; Tran, H; Zhang, J; Gibbons, DL; Wargo, J; Kim, BYS; Heymach, JV; Mendez-Gomez, HR; Jiang, W; Sayour, EJ; Lin, SH;
Details: Publication Year 2025-11,Volume 647,Issue #8089,Page 488-497
Journal Title: Nature
Publication Type: Research article
Abstract: Immune checkpoint inhibitors (ICIs) extend survival in many patients with cancer but are ineffective in patients without pre-existing immunity(1-9). 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 processes(10-14). 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.
Keywords: Humans; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology/administration &; dosage; B7-H1 Antigen/immunology/metabolism; *Neoplasms/immunology/drug therapy/therapy; *COVID-19 Vaccines/immunology/administration & dosage; CD8-Positive T-Lymphocytes/immunology; Animals; *SARS-CoV-2/immunology/genetics; Female; Mice; *Cancer Vaccines/immunology; Interferon Type I/immunology/metabolism; mRNA Vaccines/immunology; COVID-19/prevention & control/immunology; Male; Vaccines, Synthetic/immunology; Immunity, Innate/drug effects; Retrospective Studies; Antigens, Neoplasm/immunology
Department(s): Haematology
Publisher's Version: https://doi.org/10.1038/s41586-025-09655-y
Open Access at Publisher's Site: https://doi.org/10.1038/s41586-025-09655-y
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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