Issues

Cyclin-dependent kinases 4 and 6 (CDK4/6) drive cellular proliferation in a number of cancers, including breast cancer and melanoma, and it has been recently shown that CDK4/6 inhibitors also promote antitumor immunity. Two studies by Lelliott and colleagues and Heckler, Ali, and colleagues showed that inhibition of CDK4/6 promoted memory T-cell differentiation by distinct, tumor type–specific mechanisms. Lelliott and colleagues showed that CDK4/6 inhibitors induce an intratumoral CD8⁺ T-cell memory phenotype in an RB-dependent, T cell–intrinsic manner and enhanced the persistence and antitumor efficacy of CAR T cells in melanoma. Heckler, Ali, and colleagues found that CDK4/6 inhibitors promoted a memory T-cell phenotype via induction of Mxd4 transcription, resulting in increased competition with MYC for MAX binding and thus loss of MYC-mediated repression of the T-cell memory phenotype in breast cancer. For more information, see the articles by Lelliott and colleagues on page 2582 and Heckler, Ali, and colleagues on page 2564.