Is the combination of immunotherapy with conventional chemotherapy the key to increase the efficacy of colorectal cancer treatment?

Figure 3 The tumor microenvironment favors or does not allow the access of both classical and nonclassical immune checkpoint inhibitors to their targets in immune cells. A: The classical immune checkpoint inhibitor (ICI) antibody cannot access its target because immune cells are surrounded by tumor cells, although immune cells may express classical ICIs; B: On the other hand, classical ICIs probably have access to immune cells but may not express the targeting molecules; C: Chemotherapy can induce the death of tumoral cells, favoring the formation of neoantigens that may reactivate immune cells. Additional classical ICI antibodies target individual molecules such as cytotoxic T-lymphocyte-associated protein 4, programmed cell death 1, and programmed cell death ligand 1; D: Finally, immune cells expressing nonclassical ICIs could have effector profiles such as helper T type 1 cells, cytotoxic T cells, M1, or N1 when nonclassical antibodies target them. Additionally, tumor epithelial cells may likely express both classical and nonclassical ICIs. ICI: Immune checkpoint inhibitor.