Meriem Bahri and colleagues have developed an orally available, small-molecule inhibitor that targets heme oxygenase 1 enzyme (HO-1) in a subset of tumor-associated macrophages that reside near the vasculature. The inhibitor treatment along with chemotherapy reduced tumor growth in mouse models of breast cancer and sarcoma. The findings suggest a way to target this population of immunosuppressive cells therapeutically, the researchers conclude. The inhibitor drug targets perivascular tumor-associated macrophages (PvTAMs) that express the LYVE-1 receptor. These cells rely on heme oxygenase to maintain an immunologically “cold” tumor — one that doesn’t trigger a strong immune response and has few tumor-infiltrating CD8+ T cells. Non-specific targeting of tumor-associated macrophages has not been an effective antitumor strategy, so Bahri et al. looked for a way to target this specific cell population instead. The KCL-HO-1i inhibitor developed by the team improved the effects of the chemotherapeutic agents gemcitabine or 5-fluorouracil to reduce tumor growth in mice, and the combination allowed more CD8+ T cells to infiltrate the tumors compared with chemotherapy alone.

The 48th Annual UNC Lineberger Scientific Symposium, is a day-and-a-half meeting exploring advances across the cancer research continuum—from molecular discovery to clinical application to population impact—that are improving cancer outcomes. The meeting features 16 talks by leaders in cancer research that bridge basic, translational and population sciences.