ABSTRACT
Over the last few years, we have gained insights into how immunotherapy, including checkpoint blockade, modulates key CD4 and CD8 T cell subsets in anti-tumor immunity. This information can now give us insights intohow immunotherapy can impact immunity in the setting of COVID-19. Indeed, we recently demonstrated that cancerpatients with T cell depletion have high COVID-19 mortality despite adequate B cell and antibody production, highlighting the importance of cellular immunity. Conversely, in the setting of B cell depletion by anti-CD20 therapy, CD8 T cells can compensate for impaired humoral immunity. PD-1 blockade increases the activation and proliferation of CD4 T follicular-helper cells, which plays a key role in promoting B cell responses and qualityantibody production. Thus, it is possible that PD-1 blockade enhances the efficacy of SARS-CoV-2 vaccination. However, PD-1 blockade in melanoma patients was actually associated with at 2-fold decrease in SARS-CoV-2specific antibodies and neutralizing antibodies, compared to a healthy donor cohort. PD-1 blockade was alsoassociated with depletion of memory CD4 T cells, suggesting there may be consequences to prolonged PD-1blockade.