Abstract 4740: CLEVER-1 as a marker to identify breast cancer patients under immunosuppression

Abstract

Abstract TAMs are the main innate immune cells regulating tumor growth and metastasis. In tumors, TAMs exhibit an immunosuppressive M2 phenotype attenuating anti-tumor immune responses. CLEVER-1 is a multifunctional scavenger receptor specifically expressed on a subset of M2 macrophages and human monocytes. Interestingly, a subset of CLEVER-1+ monocytes and TAMs are increased in conditions where immunosuppressive functions prevail, like pregnancy and cancer. In addition, high CLEVER-1 mRNA levels associates with poorer overall survival of breast cancer patients. Therefore, we want to investigate can CLEVER-1 be used as a surrogate marker for identifying cancer patients under immunosuppression. Since we detected CLEVER-1+ TAMs in 40% of breast cancer patients, we will characterize whether the amount of CLEVER-1+ TAMs in tumor biopsy samples correlates with the number of CLEVER-1+ monocytes in breast cancer patient blood. We will collect blood, plasma, healthy breast tissue and tumor tissue from 200 newly diagnosed treatment naive breast cancer patients. The tissue samples and the blood from each patient are characterized by flow cytometry to identify the activation status of monocyte and macrophage populations in relation to CD4/CD8, Th1, Th2, Th17 and Treg populations. By now, we have received 25 patient samples from which 12 have been initially analyzed for CLEVER-1 expression in the peripheral blood together with other immune cell populations. Our preliminary data show that CLEVER-1 expression on peripheral blood monocytes is increased in breast cancer patients who have higher levels of Tregs. Additionally, the amount of CD4+ effector T cells (Th1 and Th17) was decreased among patients, whereas the amount of Th2 CD4+ cells was increased when comparing to the blood of healthy volunteers. The abnormal Th1/Th2 ratio is linked to cancer progression. The expected outcome is that CLEVER-1 could be used as a surrogate marker to identify patients under immune suppression. These patients could benefit from anti-CLEVER-1 therapy or other clinically available immunomodulatory drugs (e.g. anti-CTLA-4; ipilimumab, anti-PD1; nivolumab). Citation Format: Reetta E. Virtakoivu, Pia Boström, Riitta Aaltonen, Ilkka Koskivuo, Sirpa Jalkanen, Maija Hollmén. CLEVER-1 as a marker to identify breast cancer patients under immunosuppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4740.