release inflammatory cytokines, which can also cause damage to neurons. Cancer Antibodies against MARCO have been shown to slow growth and metastasis in syngeneic mouse tumor models, by reprogramming immunosuppressive (M2)-like TAMs into inflammatory (M1)-like macrophages. This switch involves changes to the metabolic program of the macrophages and activation of NK cells. In addition, targeting MARCO on human macrophages repolarizes TAMs and restores the cytotoxic, anti-tumor capacities of NK and T cells. These findings indicate that strategies that target MARCO-expressing TAMs to remodel the immune-suppressive tumor microenvironment might be developed for cancer therapy. In non-small-cell lung cancer (NSCLC) tissues, researchers found an association between expression of MARCO mRNA and genes that regulate immune response pathways, including immunosuppressive TAMs, T-cell infiltration, and immune checkpoint molecules. Higher infiltration of tumor tissues by macrophages was seen in tumors expressing PD-L1; macrophages within tumor cell nests co-expressed MARCO and PD-L1. MARCO is therefore a target of immune therapeutic strategies to inhibit TAMs in NSCLC, possibly in combination with immune checkpoint inhibitors. In patients with renal cell carcinoma or colorectal cancer, those with tumors that expressed low levels of MARCO had longer survival times than patients whose tumors expressed high levels of MARCO. Additionally, high MARCO levels are observed in patients with melanoma that is refractory to checkpoint inhibitor therapy, and patients with solid tumors refractory to chemotherapy. References Further reading Scavenger receptors