CDK4/6 blockade provides an alternative approach for treatment of mismatch-repair deficient tumors.

ABSTRACT: Mismatch repair-deficient (dMMR) tumors show a good response toward immune checkpoint inhibitors (ICI), but developing resistance impairs patients' outcomes. Here, we compared the therapeutic potential of an α-PD-L1 antibody with the CDK4/6 inhibitor abemaciclib in two preclinical mouse models of dMMR cancer, focusing on immune-modulatory effects of either treatment. Abemaciclib monotherapy significantly prolonged overall survival of Mlh1^-/- and Msh2^{loxP/loxP;TgTg(Vil1- cre)} mice (Mlh1^-/-: 14.5 wks vs. 9.0 wks (α-PD-L1), and 3.5 wks (control); Msh2^{loxP/loxP;TgTg(Vil1- cre)}: 11.7 wks vs. 9.6 wks (α-PD-L1), and 2.0 wks (control)). The combination was not superior to either monotherapy. PET/CT imaging revealed ind

SUBMITTER: Salewski I 

PROVIDER: S-EPMC9278458 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature