Human chorionic gonadotropin induces melanoma growth

QADRANA, FLORENCIA M; NICOLA CANDIA, ALEJANDRO J.; VALEFF, NATALíN ; JURIOL, LORENA; HEGER, JULIA; VENTIMIGLIA, MARíA SILVIA; ABELDAñO, ALEJANDRO; CANDOLFI, MARIANELLA; JENSEN, FEDERICO

Congreso; Reunión conjunta de sociedades de biociencias; LXVI Reunion anual de la Sociedad Argentina de Inmunologia (SAI); 2018

Melanoma is the leading cause of neoplasia inwomen within reproductive age and the most frequently diagnosed malignancyduring pregnancy. However, the physiological mechanism behind this phenomenonremains unknown.We aimed to investigate here the role ofpregnancy-associated hormone, human chorionic gonadotropin (hCG), in melanomabehavior.Mouse metastatic melanoma cell line (B16-F10) wascultured with hCG (10 IU) or PBS for 24, 48 and 72 h. Proliferation rate was evaluatedby flow cytometry (FC) using CFSE staining. Besides, expression levels of PD-L1and PD-1 on B16-F10 cells were also measured by FC. Each experiment wasperformed in duplicates and repeated three times. Additionally, virgin 8-10weeks old C57BL/6 females were subcutaneously injected with 2X105B16-F10 cells and challenged (IP) every second day with hCG (10 IU) or PBS (n=6each group). Tumor volume was daily monitored and animals were sacrificed 22days after tumor injection. Tumor and spleen tissues were dissected weightedand mechanically disaggregated using 70-ìm nylon filters. Obtained cells were stained with specificantibodies against CD45, CD3, CD19, CD4, CD8, Foxp3, NK.1.1, CD11c, PD-1, PD-L1and analyzed by FC. Mann. Whitney or t-tests were applied to compare groups.We observed that hCG treatment neither affectsproliferation rate nor provoked changes on PD-1/PD-L1 expression in B16-F10cells in vitro. However, tumor-bearingfemale mice treated with hCG depicted a significantly higher tumor volume and tumorweight as compared to PBS-treated control mice. Furthermore, hCG-treated mice showedsignificantly lower numbers of tumor infiltrating leukocytes (TIL) as comparedto control animals. Systemically, hCG-treated mice showed significantly lowerpercentages of CD19+ B and CD3+ T lymphocytes in thespleen. Additionally, splenic CD3+CD8+ T cells expressedhigher levels of PD-1 compared to controls.Our results clearly demonstrate that pregnancy-associatedhormone (hCG) induces melanoma growth by a mechanisms involving host immunesystem regulation.