Abstract Dabigatran etexilate, an FDA approved thrombin inhibitor, has been used for treatment of venous thromboembolism for many years in cancer patients, including prostate cancer patients. Beyond its anticoagulant properties, the anti-prostate cancer properties and immunomodulatory capacity of dabigatran etexilate remain largely uncharacterized. Therefore, this study aims to determine the anti-tumor effects of dabigatran etexilate alone and its combination with anti-CTLA4 antibody in a syngeneic mouse model of MyC-CaP cells. Mice bearing MyC-CaP xenograft tumors received dabigatran etexilate daily via oral gavage and/or anti-CTLA4 antibody treatments every other day through intraperitoneal injection for 14 days. Tumor volumes were monitored throughout the treatments, after which fresh tumor tissues were dissected for flow cytometric characterization of tumor-infiltrating lymphocytes (TILs). The combination of dabigatran etexilate and murine anti-CTLA4 blocking antibody resulted in significantly enhanced anti-tumor efficacy, achieving 18% greater tumor growth inhibition compared to anti-CTLA4 monotherapy alone, and markedly prolonged overall survival of tumor bearing mice. Flow cytometry analysis revealed that dabigatran etexilate in combination with anti-CTLA4 antibody significantly increased effector T cell (Teff) populations while reducing regulatory T cells (Tregs). Notably, granzyme B-positive cytotoxic CD8+ T cells increased by 1.6 folds in the combination group compared to anti-CTLA4 monotherapy. In addition, granulocytic myeloid-derived suppressor cells (Gr-MDSCs) were significantly reduced in the combination group. Furthermore, single-cell analysis of tumor-infiltrating lymphocytes revealed that dabigatran etexilate and anti-CTLA4 combination therapy markedly increased cytotoxic natural killer (NK) cell infiltration while decreasing suppressive and exhausted NK cell populations. Taken together, our data has shown that dabigatran etexilate potentiates anti-CTLA4 therapy by activating cytotoxic T and NK cells while suppressing immunosuppressive Tregs and Gr-MDSCs. These results suggest that dabigatran etexilate deserves further investigation as a new immunomodulatory agent for prostate cancer prevention and treatment. Citation Format: Liankun Song, Matthew Gozon, Andrewtrung Le, Jun Xie, Xiaolin Zi. Dabigatran etexilate potentiates the anti-tumor effects of anti-CTLA4 antibody through remodeling the immune microenvironment in a syngeneic mouse model of MyC-CaP cells abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 954.
Song et al. (Fri,) studied this question.