In summary, our data delineate a novel immunological mechanism through which γδ T cells recruited to the TME of HR+HER2− mammary tumors upon CCL2 secretion as driven by CDK4/6 inhibitors promote the IL17-dependent repolarization of TAMs toward a CX3CR1+ profile associated with resistance to therapy (Figure 1). The gene discussed is CX3CR1; the disease is breast cancer.