Description

A novel pathological role of IL-34 in cancer

Muhammad Baghdadi, Haruka Wada, Ken-ichiro Seino*

Hokkaido University, Sapporo, Japan

*Corresponding author

The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD1 address these issues in part, clinical responses remain limited to a subpopulation of patients. Recently, we identified interleukin-34 (IL-34) produced by lung cancer cells as a driver of chemoresistance. In particular, we found that IL-34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant lung cancer cells by activating AKT signaling. Targeting IL-34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. We have further observed that the expression of IL-34 in other solid and hematological cancers. Our data define a novel pathogenic role for IL-34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy.

Reference

Baghdadi, et al. Chemotherapy-induced IL-34 enhances immunosuppression by tumor-associated macrophages and mediates survival of chemoresistant lung cancer cells. Cancer Res 76: 6030-6042, 2016