Gene

Cancer

Internal medicine

Downregulation and upregulation

Cytotoxic T cell

Granzyme

In vitro

Immunology

Perforin

T cell

Dendritic cell

Granzyme B

Cancer research

Breast cancer

Biochemistry

Medicine

Biology

Immune system

Cancer Cell

Intratumoral CD103+ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103+ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8+ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors. Gene expression analysis identified upregulation of Cxcl9 within intratumoral DCs during combination therapy, and therapeutic efficacy was ablated by CXCR3 blockade, Batf3 deficiency, or Irf8 deficiency.

TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer