Support for the hypothesis that successful immunotherapy of various cancers can be achieved by inhibiting a progesterone associated immunomodulatory protein

Med Hypotheses. 2009 Jan;72(1):87-90. doi: 10.1016/j.mehy.2008.05.042. Epub 2008 Oct 7.


A hypothesis was proposed that cancer cells may utilize a pre-existing mechanism that pregnant mammals use to avoid natural killer cell immune surveillance of the fetus. The hypothesis suggested that those cancer cells that are able to proliferate may have found a way to cause the expression of the immunomodulatory protein known as the progesterone induced blocking factor (PIBF). The cancer cells could find an alternate pathway to make this protein that does not require progesterone secretion, or the cancer cells may actually utilize progesterone and thus make PIBF in a similar fashion to normal pregnancy. If the former mechanism was operational, then one could develop monoclonal antibody type therapy directed to this unique protein not needed for normal body functions. However, if the latter pathway involving progesterone secretion is operational, then there would be drugs already on the market, e.g., the progesterone receptor antagonist mifepristone that could be used to treat these cancers. In vitro data has shown that 100% of human leukemia cell lines express mRNA for the PIBF protein. Some leukemia cell lines have been found that actually express the PIBF protein. In fact adding progesterone to the culture media upregulated PIBF protein expression and mifepristone inhibited it. Controlled studies in various murine spontaneous cancers not known to be associated with progesterone receptors showed increased length and quality of life following mifepristone therapy. Anecdotal improvement in advanced widely metastatic human cancers has also been found. Thus there is now experimental data to support this hypothesis and a new door to a completely different type of cancer therapy has been opened.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Immunologic Factors / physiology*
  • Immunotherapy / methods*
  • Lung Neoplasms / drug therapy
  • Mice
  • Mifepristone / therapeutic use
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • Neoplasms / therapy*
  • Pregnancy Proteins / genetics
  • Progesterone / antagonists & inhibitors*
  • RNA, Messenger / genetics
  • Receptors, Progesterone / drug effects
  • Receptors, Progesterone / physiology
  • Suppressor Factors, Immunologic / genetics


  • Immunologic Factors
  • PIBF1 protein, human
  • Pregnancy Proteins
  • RNA, Messenger
  • Receptors, Progesterone
  • Suppressor Factors, Immunologic
  • Mifepristone
  • Progesterone