Reversal of dysfunction of dendritic cells induced by Treg cells for enhancing cancer immunotherapy

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B150
Abstract ID: 4340

Presenting Author:
Xia Liu , Assistant Professor at Washington Univ. Sch. of Med., St. Louis

Abstract:

Different types of Regulatory T (Treg) cells create immunosuppressive microenvironments in cancer patients, which are a major obstacle to effective antitumor immunity. A precise understanding of the molecular mechanisms utilized by Treg cells for immune suppression on different types of immune cells is critical for the development of effective strategies for cancer immunotherapy. We investigated the interaction between breast cancer tumor-derived gamma-delta Treg cells with dendritic cells (DCs) and determined the phenotypic and functional changes of DCs. We showed that tumor-derived gamma-delta Treg cells promote the development of senescent DCs with tolerogenic functions in breast cancer. In addition, we demonstrated that PD-L1 and STAT3 signaling pathways are involved in senescence induction in DCs mediated by gamma-delta Treg cells. Importantly, our complementary in vivo studies further demonstrated that blockages of PD-L1 and STAT3 signaling can prevent gamma-delta Treg-induced senescence and reverse tolerogenic functions in DCs, as well as enhance anti-tumor immunotherapy in the human breast cancer models. These studies not only dissect the suppressive mechanism mediated by tumor-derived gamma-delta Treg cells but also provide novel strategies to enhance anti-tumor efficacy mediated by tumor-specific T cells for cancer immunotherapy.