Immunocompetent and immunocompromised cancer populations: Post-vaccination humoral and cellular immune responses against SARS-CoV-2.
Authors: Titova Elizabeth , Kan Veronica W , Ip Andrew , Lozy Tara , Shier Kileen , Prakash Vittal P , Starolis Meghan , Ansari Sara , Goldgirsh Kira , Kim Seoyeon , Pelliccia Michael C , Mccutchen Aamirah , Megalla Martinus , Gunning Thomas S , Kaufman Harvey W , Meyer William A , Perlin David S 
Published: June 2023

e18779 Background: Cancer patients are at risk for severe COVID-19 outcomes due to an impaired immune response amongst other factors. However, the immunogenicity of SARS-CoV-2 vaccination is poorly characterized in this population. We hypothesized that cancer versus non-cancer individuals would mount less robust humoral and/or cellular immune SARS-CoV-2 responses. Methods: Among 594 vaccinated individuals with varying COVID-19 statuses (ie, not known to have been infected, previously infected, or with Long COVID), receptor binding domain (RBD) and total spike protein antibody levels, as well as T cell responses were assessed in non-cancer healthy individuals (n=479), non-cancer immunocompromised individuals (n=35), and cancer patients with hematologic malignancies or carcinomas (n=80). Among cancer patients, 85% (n=68) had an underlying hematologic malignancy with 62% (n=42) receiving B-cell depleting treatments at one point pre-blood collection and 43% (n=18) ≤30 days pre-blood collection. RBD antibody responses were measured using the HMH-CDI RUO SARS-CoV-2 RBD ELISA Assay. CD4+ and CD8+ T cell reactivity was measured with the QuantiFERON SARS-CoV-2 RUO Starter and Extended Pack Test. Results: 98% (n=469) of non-cancer and 76% (n=61) of cancer individuals had RBD antibody titers >999 U/mL, and of these, 60% (n=282) non-cancer and 43% (n=26) cancer individuals had elevated T cell responses - indicating most vaccinated individuals mounted robust cellular and/or humoral responses. Robust antibody and elevated T cell responses strongly correlated in the non-cancer cohort but not in the cancer cohort. Composite T cell responses were higher in individuals previously infected with SARS-CoV-2 or diagnosed with Long-COVID compared to uninfected individuals. A difference ( P<0.001) was found between T cell responses in non-cancer healthy (n=479) and carcinoma (n=12) cohorts but not between non-cancer healthy and hematologic malignancy (n=68) cohorts, with the highest T cell responses observed in the non-cancer healthy cohort followed by the hematologic malignancy cohort, and lastly the carcinoma cohort. Conclusions: No prominent correlation was seen between antibody and T cell levels in the cancer cohort likely due to the effect of B-cell targeted therapies that suppress antibody responses. The study supports a suppressive role of B cell targeted therapies in blood cancer patients on antibody responses, but not on T cell responses to SARS-CoV-2 vaccination. Interestingly, we found T cell responses to have wide variation in the hematologic malignancy cohort, likely reflective of the highly dysregulated T cell phenotype in certain liquid tumors such as CLL patients. SARS-CoV-2 vaccination continues to be an effective way to induce humoral and cellular immune responses, a key preventive measure against infection and/or subsequent more severe adverse outcomes.