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

Figure 2 Mechanism of action using either anti-programmed cell death ligand 1 or anti-nonclassical immune checkpoint inhibitor antibodies to increase the effector immune response in colorectal cancer. A: The programmed cell death ligand 1 molecule expressed on both tumor and myeloid suppressor cells interacts with programmed cell death 1 molecules expressed on exhausted CD8⁺ and CD4⁺ T cells, inducing a state of anergy. Additionally, other nonclassical immune checkpoint inhibitor molecules can induce anergy in T cells; B: Anti-programmed cell death ligand 1 antibodies block the interaction of the programmed cell death 1/programmed cell death ligand 1 axis, favoring the return from the state of anergy to exert the effector function of CD4⁺ and CD8⁺ T cells, favoring the reduction of the tumor burden. Most likely, nonclassical immune checkpoint inhibitor antibodies may have a similar effect; C: Once CD4⁺ T cells are activated, they produce cytokines for the efficient activation of CD8⁺ T cells, which in turn produce granzyme and perforin, inducing apoptosis in tumor cells. The addition of chemotherapeutic drugs increases the induction of neoantigens, favoring immune response activation. PDL1: Programmed cell death ligand 1; PD1: Programmed cell death 1; ICI: Immune checkpoint inhibitor.