Targeting Tumor-Promoting Myeloid Cells in Colon Cancer To Improve Anti-Tumor Immunity

Abstract

Colon cancer is the second leading cause of cancer mortality worldwide. Over the past decade, immunotherapy has become an important treatment type for many cancers, including colon cancer. However, not all colon cancer patients respond effectively due to their highly immunosuppressive tumor microenvironment (TME). Therefore, novel targets for immunotherapy should focus on reducing the immunosuppression in colon cancer. Tumor-infiltrating myeloid cells can become tumor-promoting because of interactions with other cells within the TME and therefore provide interesting target options. The three most common types of tumor-promoting myeloid cells in colon cancer are tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs) and myeloid-derived suppressor cells (MDSCs). They are generally known for their repression of the immune system and their promotion of cancer progression. This review aims to identify the most promising targets on tumor-promoting myeloid cells in colon cancer by investigating the recruitment, polarization, activation and immunosuppressive function of tumor-promoting myeloid cells. The most promising targets were the upstream receptors CSF1R and CD300ld of the STAT3 pathway and the myeloid immune checkpoints VISTA and SIRPα in and on tumor-promoting myeloid cells. Targeting these resulted in reduced immunosuppression and improved anti-PD-L1 outcomes.