SARS-CoV-2 vaccines sensitize tumors to immune checkpoint blockade

A new study published on Nature shows that tumors might be sensitized to immune therapies by SARS-CoV-2 mRNA vaccines, with a similar benefit in patients with immunologically cold tumours.

Poor responses to immune blockade inhibitors (ICI) are attributed to immunosuppressive tumor microenvironments and there are currently no clinically available methods to improve responses to ICI by modifying the tumor microenvironment. Authors note that there are now multiple case reports of patients whose tumors spontaneously resolved after COVID-19 mRNA vaccines; thus, they investigated effects SARS-CoV-2 mRNA vaccines on immunity in patients with non-small cell lung cancer carcinoma and melanoma, as well as in animal models and healthy volunteers. Results showed that 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 tumor-associated antigens. Although tumour cells subvert these primed responses by increasing PD-L1 expression, co-administration of ICIs sustains T cell responses and elicits epitope spreading against tumor-associated antigens. Results were confirmed in humans, including increases in type I interferon, myeloid–lymphoid activation in healthy volunteers and PD-L1 expression on tumors. Moreover, vaccination within 100 days of initiation of ICI is associated with significantly improved median and three-year overall survival in multiple large retrospective cohorts of patients with non-small cell lung cancer carcinoma and melanoma. As authors conclude, «These findings define a role for widely available vaccines for enhancing the efficacy of cancer immunotherapy. Although we focus on a single therapeutic due to its wide availability, these data could pave the way for other universal mRNA therapeutics specifically designed to reset patient immune systems for enhanced response to immunotherapy».