852: Response to Immune Checkpoint Inhibitors in Cancer and Their Effects on Monocytes in Septic Shock

Introduction: Intermediate monocytes (CD14+CD16+) can eliminate cancer cells and studies have shown that they increase significantly in patients who respond to immune checkpoint inhibitors. Monocytes are also pivotal for host response during sepsis. Increasing numbers of intermediate monocytes and low numbers of classical monocytes (CD14+CD16-) are associated with increased mortality in sepsis. Trials have evaluated ICIs to improve T-cell function/survival in sepsis, but it is unknown if prior use in cancer patients could impact monocytes and sepsis outcomes. Hypothesis: Patients with tumoral response to ICIs can have increasing circulating intermediate monocytes and worse outcomes during septic shock. Methods: 2 patients (P1/P2) with septic shock who had received ICIs for their malignancy within 10 days of ICU admission were evaluated. SOFA scores, outcomes and PBMCs were collected at the time of ICU admission and ICU discharge. Spectral flow cytometry was used to perform a comprehensive multiparameter phenotyping analysis of both lymphocytes and monocytes fractions of PBMC. Results: P1&P2 received PD-1 blockade (pembro+nivo) within 9 days of ICU admission and SOFA scores were 7 and 10 respectively. P1, who had minimal tumoral response to the ICI, showed low intermediate monocytes (1.4%) at the time of ICU admission. P2 who had significant tumoral response to the ICI, had higher intermediate monocytes (11.4%). The frequency of classical monocytes (3.8% and 5%) was similar in both patients at the time of ICU admit. At the time of ICU discharge, P1 was alive and had decreasing intermediate monocytes (0.3%). P2 had an almost two-fold increase (34.4%) of these cells at the time of death. Intermediate monocytes and non-classical monocytes of P2 had elevated CD69 expression compared to P1 suggesting greater activation. Lymphocytes were similar among both. Expression of inhibitory molecules (PD-1, CTLA-4, TIM-3) on CD4+ T-cells, (poor outcomes in sepsis), were similar for both. Conclusions: Prior treatment with ICIs could affect intermediate monocyte’s function and outcomes during septic shock. Preliminary data suggest that in patients who develop sepsis and have received ICIs, evaluation of monocytes should be considered prior to contemplating the use of ICIs to enhance T-cell function during sepsis.