SITC 2022 | The role of myeloid cells in TME

Judith Varner, PhD, University of California, San Diego, CA, discusses the role of myeloid cells in the tumor microenvironment (TME) and the antitumor activity of inhibiting PI3K gamma. Once a tumor reaches a certain stage in development, an angiogenic switch, also called an inflammation switch, occurs whereby numerous macrophages, granulocytes and monocytes are recruited into the tumor. Due to the TME being hypoxic and metabolically unfavorable for macrophage development, most of the myeloid cells are immunosuppressive and secrete numerous factors that can inhibit T-cell recruitment and promote matrix production in fibroblasts. This provides a barrier to T-cell recruitment and promotes angiogenesis and tumor metastasis through the secretion of various cytokines. Strategies to combat this response include inhibiting the myeloid response in tumors through blocking cytokines and altering the transcriptional state or repolarizing the cells to promote T-cell activation. Inhibiting PI3K gamma prevents myeloid cells from attaching to the endothelium and entering into tumors and additionally promotes repolarization of those cells that have entered the tumor. Accordingly, inhibition of PI3K gamma has been shown to strongly inhibit metastasis in preclinical models. This interview took place at the 37th Annual Meeting of the Society for Immunotherapy in Cancer (SITC 2022) in Boston, MA.

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