Abstract P063: Tumor cell-derived lactic acid inhibit anti-tumor immunity in the immune checkpoint blockade resistant tumor

Immune checkpoint blockade therapy targeting the PD-1/PD-L1 axis, one of the most promising cancer immunotherapies, has shown remarkable clinical impact in multiple cancer types. Despite the recent success of PD-1/PD-L1 blockade therapy, acquired resistance, emerging as late relapses or recurrences, has been reported in the long-term follow-up of clinical trials. However, the resistance mechanisms of PD-1/PD-L1 blockade therapy are still unclear. Here we found that tumor cell-derived lactate rendered the immunosuppressive tumor microenvironment in the PD-1/PD-L1 blockade resistant tumors. Interestingly, increased lactate in the PD-1/PD-L1 blockade resistant tumors enhanced PD-1/PD-L1 interaction. Furthermore, combining a PD-L1-antibody-drug conjugate (ADC) with AZD3965, a MCT inhibitor eradicated the resistant tumor cells synergistically in 4T1 syngeneic murine models. Together, our results suggest a new combination treatment strategy to improve the therapeutic efficacy of immune checkpoint blockade therapies. Citation Format: Wonkyung Oh, Alyssa Min Jung Kim, Ruoxuan Sun, Seung-Oe Lim. Tumor cell-derived lactic acid inhibit anti-tumor immunity in the immune checkpoint blockade resistant tumor [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P063.