Abstract 2679: Myeloid olfactory receptors in melanoma

Abstract Olfactory receptors are commonly found in the nasal cavity and function to detectodorants. However, very recent studies have determined that innate immune cells,including monocytes and macrophages, express olfactory receptors. OLFR2 (OR6A2 inhumans), was recently linked to atherosclerosis development through interaction with itsligand, octanal. Increased levels of octanal are considered as a risk factor foratherosclerosis. Conversely, octanal levels are associated with lower cancer incidence,suggesting that OLFR2 may play a protective role in cancer. Indeed, data from TheCancer Genome Atlas for liver and brain cancers show that OLFR2 expression isassociated with increased patient survival. Here, we utilized an orthotopic melanomamouse model using B16 cancer cells in C57/BL6 mice that had been transplanted witheither wild type or OLFR2 knockout bone marrow to directly test the role of OLFR2 onimmune cells in regulating tumor growth. We found that hematopoietic deletion of OLFR2exacerbated melanoma tumor growth in these mice; again, supporting the notion thatOLFR2 is anti-tumoral. The OLFR2+ cells present in the tumor were myeloid cells.Monocytes, non-classical monocytes specifically, function to detect cancer cells in tumorseeding sites, and recruit NK cells for tumor cell destruction. OLFR2-deficientmacrophages were found to migrate less to tumor cells in an in vitro assay, suggestingthat OLFR2 is involved in the sensing of newly seeding tumor cells, likely through sensingoctanal. Studies are ongoing to determine the exact functions of OLFR2+ monocytes andmacrophages in the tumor microenvironment. OLFR2 may be one of several olfactoryreceptors that is utilized by myeloid cells as a defense mechanism for detection of newlyseeding or metastatic tumor cells. As olfactory receptors are easily druggable targets,understanding their role in cancer prevention could lead to emerging newimmunotherapies for cancer. Citation Format: Elayne M. Benson, Klaus Ley, Marco Orecchioni, Catherine C. Hedrick. Myeloid olfactory receptors in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2679.