Internal medicine

Chemokine receptor

Receptor

Suppressor

Tumor microenvironment

Immunotherapy

Myeloid-derived Suppressor Cell

Cancer

Chemokine

Immunology

CCR2

Glioma

Blockade

Myeloid

Immune checkpoint

Tumor cells

Cancer research

Medicine

Immune system

Proceedings of the National Academy of Sciences

Significance Standard of care for glioblastoma (GBM) results in median survival of &lt;15 mo with 5-y survival &lt;10%, highlighting the need for novel treatments. Immune checkpoint blockade has been successful in various cancer subtypes. However, success has not extended to GBM, largely due to the characteristically immune-suppressive glioma microenvironment. Here, we report targeting of myeloid derived suppressor cells (MDSCs), via inhibition of CCR2, unmasks efficacy of checkpoint blockade in GBM. Using checkpoint inhibitor-resistant murine glioma models, we show combination treatment reduces MDSCs and increases functional T cells within the tumors, and significantly extends overall survival. Our results support targeting of CCR2-expressing myeloid cells to enhance immunotherapies for GBM, and warrant translation of this approach to early human clinical trials.

CCR2 inhibition reduces tumor myeloid cells and unmasks a checkpoint inhibitor effect to slow progression of resistant murine gliomas