HUMAN CHORIONIC GONADOTROPIN FACILITATES MELANOMA GROWTH

NICOLA CANDIA AJ; HEGER J; ABELDAÑO A; QUADRANA F; JURIOL L; VENTIMIGLIA MS; JENSEN F; VALEFF N; ASAD AS; CANDOLFI M

Mar del Plata

Congreso; LXVI Reunion Anual de la Sociedad Argentina de Inmunologia; 2018

Melanoma is the leading cause of neoplasia in women within reproductiveage and the most frequently diagnosed malignancy duringpregnancy. However, the pathophysiological mechanisms behindthis phenomenon remain unknown.We aimed to investigate here the role of pregnancy-associated hormone,human chorionic gonadotropin (hCG), in the progression ofexperimental melanoma.Mouse metastatic melanoma cell line (B16-F10) was cultured withhCG (100 IU/ml) or PBS for 24, 48 and 72 h. Proliferation rate wasevaluated by flow cytometry (FC) using CFSE staining. In addition,the expression levels of PD-L1 and PD-1 on B16-F10 cells were alsomeasured by FC. Each experiment was performed in duplicates andrepeated three times.Additionally, virgin 8-10 weeks old C57BL/6 fe-males were subcutaneously injected with 2X105 B16-F10 cells andchallenged (IP) every other day with hCG (10 IU) or PBS (n=6 eachgroup) starting on day 1 post-tumor inoculation. Tumor volume wasdaily monitored and animals were euthanized 22 days after tumorinjection. Tumors and spleens were dissected, weighted and mechanicallydisaggregated using 70-μm nylon filters. Cells were thenstained with specific antibodies against CD45, CD3, CD19, CD4,CD8, Foxp3, NK.1.1, CD11c,PD-1,PD-L1 and analyzed by FC.Mann.Whitney or t-tests were applied to compare groups.We observed that hCG treatment neither affects proliferation ratenor provoked changes on PD-1/PD-L1 expressionin B16-F10 cellsin vitro. However, treatment with hCG accelerated B16 tumor growthin vivo. Furthermore, hCG-treated mice showed significantly lowernumbers of tumor infiltrating leukocytes (TIL) andlower percentagesof CD19+ B and CD3+ T lymphocytes in the spleen as compared tocontrol animals. Additionally, hCG treatment induced the up-regulationof PD-1 in splenic CD3+CD8+ T cells as compared to controls.Our results suggest that pregnancy-associated hormone (hCG) facilitatesmelanoma growth by mechanisms involving host immunesystem regulation.