Acquired resistance to cancer immunotherapy: Role of tumor-mediated immunosuppression

Abstract

In the tumor microenvironment (TME), tumor cells are constantly evolving to reduce neoantigen generation and the mutational burden to escape the anti-tumor response. This will lower tumor reactivity to the adaptive immune response and give rise to tumor intrinsic factors, such as altered expression of immune regulatory molecules on tumor cells. Tumor-extrinsic factors, such as immunosuppressive cells, soluble suppressive molecules or inhibitory receptors expressed by immune cells will alter the composition and activity of tumor-infiltrating lymphocytes (TILs) (by increasing T regulatory cells:T effector cells ratio and inhibiting T effector cell function) and promote tumor growth and metasta..