Immune Profiling Uncovers Memory T-Cell Responses with a Th17 Signature in Cancer Patients with Previous SARS-CoV-2 Infection Followed by mRNA Vaccination

SIMPLE SUMMARY: Cancer patients are considered a high-risk group for infectious diseases including COVID-19. The protective effects of vaccination are unclear in oncologic patients, as well as their duration. In this study antibody, T-cell and myeloid cell immunity were evaluated in three cohorts of healthy donors and oncologic patients, including those infected with SARS-CoV-2, BNT162b2-vaccinated (mRNA vaccine), and with previous COVID-19 and subsequently vaccinated. We concluded that vaccination was a poor inductor of cellular immunity towards the S protein. Memory T-cells were only detected in patients and healthy donors with COVID-19 previous to vaccination but with an accentuated Th17 inflammatory profile, together with elevated numbers of circulating neutrophils. ABSTRACT: It is unclear whether patients with cancer present inherently impaired responses to COVID-19 and vaccination due to their treatments, neoplastic diseases or both. To address this question, immune profiling was performed in three cohorts of healthy donors and oncologic patients: infected with SARS-CoV-2, BNT162b2-vaccinated, and with previous COVID-19 disease and subsequently vaccinated. Cancer patients showed good antibody responses to vaccination, but poor induction of T-cell responses towards the S protein when compared to infection. Following natural infection, the major targets for T-cells were the SARS-CoV-2 structural proteins M and S, but not the N protein. Similar to antibody titers, the T-cell responses quickly decayed after six months post-vaccination. Significant memory T-cell expansion was observed in vaccinated donors only if previously diagnosed with COVID-19 before undergoing vaccination. Oncologic patients with previous COVID-19 followed by vaccination exhibited potent IL-17+ CD4 and CD8 T-cell responses and elevated numbers of circulating neutrophils in peripheral blood.