Pre-vaccine immune profiling in cancer patients identifies correlates of COVID-19 vaccine responses

mRNA vaccines have been highly effective against SARS-CoV-2-related severe illness and are currently undergoing investigation as anti-cancer therapeutics. Our prior work has shown that patients undergoing cancer therapy have reduced immune responses to mRNA-based vaccines. Therefore, further investigation into immunologic responses in the setting of immune-altered hosts is warranted. In this study, we investigated pre-vaccination peripheral immune cell repertoire from a cohort of 66 patients with cancer on active treatment. Immune cell repertoire was characterized by mass cytometry to identify key immune subsets for COVID-19 vaccine response. Immunological populations were then assessed for their association with spike-specific antibody titers measured by ELISA and the breadth and depth of T-cell response to vaccine by TCR sequencing. Immune features significantly correlated with response were selected using an iterative bootstrapping model. We identified immunological features including abundance and functional state of T and B cells, expression of co-stimulatory and -inhibitory molecules, and presence of innate lymphoid cells, and myeloid-derived suppressor cells correlated with humoral and cellular responses. Our findings suggest that vaccine-induced immune responses could serve as biomarkers of immune fitness, in general and specifically for patients receiving anti-cancer mRNA vaccines, providing insights to tailor future therapeutic strategies for immune-altered patients.