P56: Characterizing postoperative antigen-specific T and B cell dysfunction to COVID-19 in cancer surgery patients.

Infection with COVID-19 within 30 days after surgery is associated with an increased risk of major complications, despite preoperative vaccination. In murine models, cancer antigen-specific T cells are highly dysfunctional following surgery, leading to cancer recurrence. The effect of surgery on antigen-specific T cell and B cell function has not been well studied in humans. The widespread vaccination against COVID-19 and the availability of immunological assays to measure SARS-CoV2 specific immune responses presents and ideal opportunity to evaluate the effect of surgery on the adaptive cellular and humoral immune system.

Methods:

Patients undergoing major abdominal surgery for malignancy, who had received at least 2 doses of the Pfizer BNT vaccine were included. Blood was collected at baseline (POD0) and then on postoperative day (POD) 1, 3 and 28. Peripheral Blood Mononuclear Cells (PBMC) were isolated immediately and cryopreserved for flow cytometry and functional assays, including T and B cell ELISpot for measurement of IFNγ and IgG3 respectively, in response to the RBD domain of the SARS-CoV2 spike (S) protein. Flow cytometry was used to characterize the cell surface phenotype of CD8+ T cells and intracellular IFNγ and TNFα. Serum was collected for quantification of antibody titres against the S-protein. Statistical comparisons were conducted on SAS® using the paired t-test and Wilcoxon Rank test for parametric and non-parametric data respectively.

Results:

A total of 30 patients were included in the study. Surgical stress resulted in a significant reduction in the proportion of CD3+ T cells that secreted IFNγ in response to the SARS-CoV2 spike protein on POD1 by ELISpot (90.9±56.8 spots) as compared to POD0 (181.3±72.2, p< 0.0001), which persisted on POD3 (128.5±49.2, p< 0.01), but recovered by POD28 (163.2±51.9, p=0.1). This was associated with a significant decrease in intracellular TNFα expression (p=0.01) and an increase in cell surface expression of PD-1 (p=0.03), but no change in the expression of exhaustion markers, TIM-3 or TIGIT, nor of T-bet. Surgery also significantly impaired the production of IgG antibody by CD19+ memory B cells upon stimulation with the SARS-CoV2 spike protein on POD1 (49.1±47.9 vs. 105.7±67.7 spots on POD0, p< 0.0001). There was no measurable decrease in the IgG, IgM or IgA serum antibody titers against the S-protein on POD1.

Conclusions:

Surgery results in measurable suppression of antigen-specific T and B cell responses to COVID-19, with implications for both postoperative infections and cancer recurrence.