Flipping the switch in immuno-oncology

Tumor myeloid cells are emerging as prime candidates for filling a hole in the immuno-oncology tool box, offering targets that can simultaneously release the brakes and rev up the gas in the immune system.

As immuno-oncology companies look to extend the efficacy of marketed checkpoint inhibitors by pairing them with other immunotherapies, they generally pick a combination partner that either removes a second brake from the immune system, for example by blocking another checkpoint protein, or that directly activates immune cells, by amplifying proinflammatory signaling.

A single compound that simultaneously does both could increase efficacy without layering on toxicities.

Because myeloid-derived immune cells represent a major source of immunosuppression in tumors, they are a growing focus among the new strategies in cancer immunotherapy.

In the majority of tumor types, the most abundant myeloid-derived cells are tumor-associated macrophages (TAMs) and monocyte-derived suppressive cells (MDSCs); myeloid dendritic cells (mDCs) can also contribute to the immunosuppressive environment.

The cells use several mechanisms to dampen antitumor T cell responses, including reducing antigen presentation and increasing expression