Key players of immunosuppression in epithelial malignancies: Tumor‐infiltrating myeloid cells and γδ T cells

Abstract

Abstract Background The tumor microenvironment of solid tumors governs the differentiation of otherwise non‐immunosuppressive macrophages and gamma delta (γδ) T cells into strong immunosuppressors while promoting suppressive abilities of known immunosuppressors such as myeloid‐derived suppressor cells (MDSCs) upon infiltration into the tumor beds. Recent findings In epithelial malignancies, tumor‐associated macrophages (TAMs), precursor monocytic MDSCs (M‐MDSCs), and gamma delta (γδ) T cells often acquire strong immunosuppressive abilities that dampen spontaneous immune responses by tumor‐infiltrating T cells and B lymphocytes against cancer. Both M‐MDSCs and γδ T cells have been associated with worse prognosis for multiple epithelial cancers. Conclusion Here we discuss recent discoveries on how tumor‐associated macrophages and precursor M‐MDSCs as well as tumor associated‐γδ T cells acquire immunosuppressive abilities in the tumor beds, promote cancer metastasis, and perspectives on how possible novel interventions could restore the effective adaptive immune responses in epithelial cancers.

Keywords

• gamma delta T cells
• immunology
• immunotherapy
• MDSCs
• tumor microenvironment
• tumor‐associated macrophages