On the basis of our findings, we speculate that ERBB2/ERBB3 mutations lead to immune escape in patients with MSS, and regorafenib can reactivate the tumor microenvironment by targeting the ERBB pathway, transforming “cold tumor” into “hot tumor,” thereby synergistically enhancing the therapeutic effects of anti–PD-1 antibodies. This evidence concerns the gene ERBB2 and Marinesco-Sjogren syndrome.