Abstract 4096: A pilot study was initiated to determine if the immunomodulatory protein, the progesterone-induced blocking factor (PIBF), is present in higher quantity in the sera of patients with gynecologic cancer as compared to controls without cancer
Authors: Check Jerome H. , Sarumi Mojirayo , DiAntonio Ann , Hunter Krystal , Simpkins Gunda , Duroseau Marie 
Published: May 2015

PIBF is a unique protein that is secreted by gamma/delta T cells and precipitously rises in the sera following progesterone (P) exposure. The 34 kDa protein protects the fetal semi-allograft from immune surveillance by reducing cytoxicity of natural killer (NK) cells by stabilizing perforin granules. The parent 90 kDa form occupies a centrosomal position close to BRCA-1. PIBF can be found in most rapidly dividing cells. One study found an over-expression of the mRNA for the PIBF protein in all 29 leukemia cell lines tested. The P receptor antagonist mifepristone was found to down-regulate PIBF protein. Mifepristone provided significant palliative benefit to a large variety of spontaneous murine and human cancers. P could also be responsible for converting the 90 kDa parent form to a 34-36 kDa split variant in the cytoplasm which may be the immunosuppressive form in cancer cells. Alternatively, some P-like secretion by the tumor could influence gamma/delta T cells in the tumor microenvironment to secrete PIBF and possibly spill over to the sera. The aim of this study was to determine if there is any increase in serum PIBF in women with gynecologic cancer as opposed to controls. Serum was obtained from women about to have surgery for gynecologic problems including malignant and benign disorders. The samples would then be measured for PIBF using a new non-commercial enzyme linked immunoabsorbent assay (ELISA) for PIBF and serum progesterone. The PIBF levels (ng/mL) from lowest to highest in women with various gynecologic cancers (in all cases serum progesterone (P) &lt;2ng/mL) were 10.06, 17.35, 32.59, 35.62, 54,7, and 57.17. The average serum PIBF was 34.6 ng/mL. There were 3 women with benign gynecologic tumors and the serum PIBF was 14.76, 15.7, and 36.64 their average serum PIBF was 22.5 ng/mL). There were 2 women with no tumors having gynecologic surgery and their serum PIBF levels (ng/mL) were 9.56 and 35.27 (with an average of 22.4 ng/mL). At least for gynecologic cancers if PIBF is conferring immune protection it is more likely operating through its intracytoplasmic presence rather than working through sera levels. In women or men exposed to exogenous or endogenous P for just 6 days it is not unusual to see sera PIBF rise to 300 to &gt;800ng/mL.

Citation Format: Jerome H. Check, Mojirayo Sarumi, Ann DiAntonio, Krystal Hunter, Gunda Simpkins, Marie Duroseau. A pilot study was initiated to determine if the immunomodulatory protein, the progesterone-induced blocking factor (PIBF), is present in higher quantity in the sera of patients with gynecologic cancer as compared to controls without cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4096. doi:10.1158/1538-7445.AM2014-4096