Our findings that CDK4/6 inhibitors prevented T cell exhaustion phenotypes via reducing PD-1, NFATc1, TOX, and CTLA-4 expression levels and MDSC numbers demonstrate that high dNLRs reflect active immune suppression with progressive T cell exhaustion in the tumor microenvironment, which is largely alleviated by CDK4/6 inhibitor treatment. Here, TOX is linked to neoplasm.