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.

Previous studies have shown differing immune responses in cancer patients towards natural infection and vaccination compared to healthy individuals. Therefore, it is yet unclear whether cancer patients show differential responses to SARS CoV-2 natural infection and vaccination with current mRNA vaccines. Immune profiling was performed in three cohorts of healthy donors and oncologic patients: infected with SARS CoV-2, BNT162b2-vaccinated, and vaccinated with previous SARS CoV-2 infection. Vaccine was found to be a poor inductor of S-specific T cell responses compared to natural infection, which acted as a potent adjuvant for vaccination in antibody and T cell responses. Antibodies towards the M protein were a biomarker of disease severity, while the major targets for T cell responses in natural infection were the M and S protein, but not the N protein. T cell responses quickly decayed after 6 months post-vaccination. T cell profiling showed that vaccination expands effector T cells rather than memory T cell subsets unless the subjects had previous COVID-19 disease. Cancer patients with previous COVID-19 and subsequently vaccinated exhibited exacerbated CD8 responses, with elevated IL-17 CD4 and CD8 T cell subsets, and neutrophils. Concluding, a previous COVID-19 infection has potent adjuvant effects for vaccination leading to memory T cell differentiation, but with enhanced inflammatory responses in cancer patients.