225P Impact of cyclin inhibitors (CDK4/6i) on immune cell populations in first-line treated metastatic breast cancer (mBC) patients

CDK4/6i plus endocrine therapy (ET) is the standard of care for first-line therapy in hormone receptor-positive (HR+)/HER2-negative (HER2−) mBC. However, resistance mechanisms appear and responses to this schedule may vary. Exceptionally, some patients still respond after 36 months. In addition, we previously showed that some cell populations such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Treg) may be promising targets in mBC patients. Here, we show the evolution of circulating MDSCs, Tregs, natural killer (NK) cells and CD4-CD8- T gamma-delta (γδ)-like cells in a cohort of long-term responder (progression-free survival >36 months) mBC patients treated with CDK4/6i-based therapies. Thirty-one HR+/HER2- mBC patients received CDK4/6i as first-line treatment and 6 of them (19%) were long-term responders. MDSCs, Tregs, NK cells and γδ-like cells from peripheral blood were analysed by flow cytometry before (baseline), during (cycle 3) and after treatment (cycle 6), and after 36 months. In long-term responders, circulating suppressive cell populations such as granulocytic (G-)MDSCs, Tregs and CD4-CD8-T γδ-like cells significantly decreased during treatment after 36 months, while NK cells significantly increased in these patients (p<0.05), as shown in the table Depletion of both total and monocytic (M-)MDSCs occured, but it was no significant (p>0.05). Cell populations in long-responder HR+/HER2- mBC patients during CDK4/6i therapy. Data are median and 95% confidence interval.Table: 225PBaselineCycle 3Cycle 6>36 monthsP-value (Friedman test)Total MDSCs37.6 (9.3-81.8)19.2 (2.3-19.8)4.7 (1.7-49.2)19.5 (5.0-112-0)0.0558M-MDSCs28.4 (6.6-65.4)15.6 (1.9-18.7)4.3 (0.7-45.7)18.5 (5.0-111.0)0.1268G-MDSCs14.1 (2.7-34.5)1.0 (0.4-8.5)1.0 (0.3-3.5)0.9 (0.08-1.0)0.0007*Tregs53.9 (18.7-67.8)24.1 (4.0-30.4)16.8 (2.8-31.8)10.5 (2.0-35.0)0.0321*γδ-like cells77.5 (23.4-151.9)18.8 (13.3-26.6)14.6 (0.0-139.3)6.4 (0.0-75.0)0.0096*NK cells186.4 (69.6-452.8)88.0 (39.9-391.5)260.0 (116.8-378.1)689.5 (259.0-2142)0.0028**, statistically significant differences (p<0.05). Open table in a new tab *, statistically significant differences (p<0.05). First-line CDK4/6i in long-term responder HR+/HER2- mBC patients may have immunomodulatory effects due to the variations occurred in the cell populations, especially the depletion of immunosuppressive cells. All cell populations may be considered as promising biomarkers of response to CDK4/6i in mBC with potential for monitoring clinical evolution.