Fig. 5.

Immunostimulation by sotorasib acting on the tumor microenvironment. Sotorasib is a highly selective inhibitor of KRAS-G12C that reacts with mutant cysteine at position 12 by connecting to a structural feature called the switch II pocket. Sotorasib can induce the production of chemokines, such as C-X-C motif chemokine ligand 10 (CXCL10) and CXCL11, as well as the release of damage-associated molecular patterns (DAMPs), leading to dendritic cell (DC) maturation and activation. The priming of naive T cells to generate cytotoxic T lymphocytes (CTLs) requires mature DC-mediated antigen presentation. The number and function of tumor-targeted CTLs is a prerequisite for the immune system to attack cancer cells. However, the expression of immune checkpoint substances (such as programmed cell death protein 1 [PD-1]) limit the anticancer activity of CTLs, and the administration of anti–PD-1 antibodies reverses this process