Combination of immune checkpoint inhibition with cryoablation augments T cell activation in the tumor immune microenvironment (TIME) - it is about TIME! 2575

Description Immune checkpoint inhibitors (ICI) can enhance anti-tumor immunity, yet triple-negative breast cancer (TNBC) patient response rate is only ∼20%. Thus, ICI combination with novel approaches may improve efficacy. Cryoablation induces tumor necrosis due to freeze-thaw cycles while preserving tumor antigens. We hypothesize that cryoablation with ICI augments T cell activation at the tumor immune microenvironment (TIME) by combining increased antigen presentation and reduced immunosuppression. In a murine TNBC model, 4T1-12B cells were bilaterally injected into BALB/c mice; left (primary) tumors were cryoablated at 2 weeks, and PBS or ICI (anti-CTLA4, PD1, or PDL1) were administered 24h pre- and post-cryoablation. Right (distant) and left tumors, blood, and tumor-draining lymph nodes (TdLN) were collected a week later. Preliminary analyses showed combination with anti-CTLA4 provided superior T cell activation in the blood related to other ICI. Compared to cryoablation alone, combination with anti-CTLA4 increased the frequency of activated CD8+ T cells in both primary and distant tumors. In the TdLN, we found increased frequencies of conventional dendritic cells and activated CD4+ and CD8+ T cells. Our findings suggest combination of anti-CTLA4 with cryoablation potentiates T cell stimulation at the TdLN, resulting in higher T cell activation locally and systemically. Response to therapy might be traceable in the blood of subjects, which can be translated to clinical application. Funding Sources Supported by CH Foundation research grant and ASCO Equipment endowment to Excellence in Women’s Helath, TTUHSC. Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)