Preclinical and clinical studies have highlighted this ratio, reflective of systemic immune activation, as an emerging predictive and prognostic marker in many cancers.22–24 In melanoma, intratumoral as well as blood CD4+/CD8+ ratio has been reported to associate with response to chemoimmunotherapy or radioimmunotherapy.25 26 Our study suggests that CD4+/CD8+ ratio may also be a useful noninvasive indicator of checkpoint inhibitor plus targeted therapy benefit, pending further validation. This evidence concerns the gene CD4 and cancer.