Metabolic modulation by CDK4/6 inhibitor promotes chemokine-mediated recruitment of T cells into mammary tumors
Roman V. Uzhachenko, Vijaya Bharti, Zhufeng Ouyang, Ashlyn Blevins, Stacey Mont, Nabil Saleh, Hunter Lawrence, Chengli Shen, Sheau‐Chiann Chen, Gregory D. Ayers, David G. DeNardo, Carlos L. Arteaga, Ann Richmond, Anna E. Vilgelm
Abstract
T cells, but not Tregs, into the tumor. Mechanistically, chemokine induction is associated with metabolic stress that CDK4/6i treatment induces in breast cancer cells. Despite the cell cycle arrest, CDK4/6i-treated cells retain high metabolic activity driven by deregulated PI3K/mTOR pathway. This causes cell hypertrophy and increases mitochondrial content/activity associated with oxidative stress and inflammatory stress response. Our findings uncover a link between tumor metabolic vulnerabilities and anti-tumor immunity and support further development of CDK4/6i and immunotherapy combinations.