More than 100 years ago, Dr. John Beard observed that under the microscope, cancer cells look like cells from the earliest stage of life, the trophoblast. The trophoblast is part of the embryo, and as the embryo travels into the uterus, the trophoblast attaches to and invades the uterus. Then, the trophoblast creates a blood supply so that the growing fetus can get nutrition from the mother. Cancer cells also invade and create a blood supply.

SOURCE: Illustration from Anatomy & Physiology, Connexions Web site. Embryonic Development

 https://openstax.org/books/anatomy-and-physiology/pages/28-2-embryonic-development

    Unlike cancer, at a certain point in development, the trophoblast stops invading and matures into the placenta. Beard claimed this happens when the fetus starts making pancreatic enzymes. This, then, was the first suggestion that pancreatic enzymes could be a tool to use against cancer.

    In our book, The Trophoblast and the Origins of Cancer, Dr. Nicholas Gonzalez and I went into great detail about how the molecular mechanisms used to invade and create a blood supply are the same in both cancer cells and trophoblast cells. There is also a brief review of this in my article about pancreatic enzymes that was published in Integrative Cancer Therapies.

    However, cancer cells and trophoblast cells have another similarity; they must convince the cells of the immune system not to attack. Since the trophoblast only gets half its genes from the mother, the mother’s immune system should reject it as foreign tissue.

    The immune system in the body must be ready to destroy invaders and foreign proteins, but it also must be regulated to keep it from being overactive and attacking the body’s own tissues by mistake. Some cancer cells evade the immune system because they have large amounts of immune checkpoints on their surface. As the name suggests, immune checkpoints are signals to the immune system telling it to leave this particular cell alone.

SOURCE: AI-generated cancer cell in a varied microenvironment

    These immune checkpoints include cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). In the last decade, drugs that block these checkpoints have become available. These drugs cause the immune system to become more active, which can be both good and bad. The cancer cells are no longer protected from the immune system, but the unleashed immune system can also start attacking normal cells. This explains the side effects, sometimes catastrophic, that these medications can have.

    Reading a review article about checkpoint inhibitors recently, I realized that I did not know whether trophoblast cells use this mechanism for avoiding the mother’s immune system. Research on immune checkpoints was fairly new at the time Dr. Gonzalez and I were working on our book.

    A quick search of the literature yielded a recent review article on this very subject. Placental cells do indeed have large amounts of CTLA-4 and PD-1 on their surfaces. Research continues on this complex topic. But it looks like once again, Beard was correct in his observation that cancer cells and trophoblast cells have much in common.