In other words, is there data to support immune surveillance, i.e., that the immune system actively patrols the body looking for cancerous cells and eliminates them?
First, a brief history of the idea. According to a 2002 review on the history of Immune surveillance (1), the idea was first suggested by the Nobel Prize winning scientist,, and the acclaimed science writer, .
Burnet wrote in 1957, ‘It is by no means inconceivable that small accumulations of tumour cells may develop and because of their possession of new antigenic potentialities provoke an effective immunological reaction, with regression of the tumour and no clinical hint of its existence‘ (2) while Thomas suggested in 1959 that the primary function of cellular immunity was to protect the body from neoplastic disease and thereby maintain tissue homeostasis (3).
How could we prove immune surveillance though?
I. One way to do it is to compare tumor incidence in immunodeficient mice versus normal (wild type) mice. Such immunodeficient mice are created by genetic manipulation to have selective impairments in their capacity to mount robust and stable immune responses. If the theory is right, immunodeficient mice should be more susceptible to tumors.
- Mice whose cytotoxic T cells were impaired were less capable of controlling tumors induced by chemical carcinogens and by an oncogenic virus (4). Cytotoxic T cell function is one of the most important, if not the most important, immune system feature that kills cancerous cells. However, there is a caveat* to this study. The study team did not observe spontaneous tumors of any kind in these mice. If the immune system is indeed killing off cancerous cells all the time, such immunodeficient mice should have more spontaneous tumors.
- Mice that were genetically manipulated to completely lack T and B cells were also less capable of controlling tumors induced by chemical carcinogens (5).
*A more generalizable caveat to cancer incidence studies in immunodeficient mice is that scientists have created a great many variety of immunodeficient mice through genetic manipulation since the late 1980s and yet spontaneous cancer rates in such mice is not noticeably higher than those in normal mice, which it should be according to the immune surveillance idea.
II. What are cancer rates in humans who are immunodeficient from taking immunosuppressive drugs after an organ transplant or become immunodeficient because of an infection such as HIV?
- Epidemiologists observe increased risk for cancers in humans following a variety of organ transplants:
- Liver (6), heart (7), bone marrow (8), kidney (9).
- In fact, there is well-known increased risk of skin cancers following organ transplants. Skin squamous cell carcinomas affect ~50% of transplant recipients within 20 years of the transplant (10).
- Immunodeficiency is the hallmark of AIDS and many cancers induced by oncogenic viruses are associated with it (11). Examples include Epstein-Barr virus, Kaposi’s sarcoma (caused by human herpes virus 8) and human papilloma virus.
Thus, increased rates of cancers are observed in transplant patients on long-term immunosuppressive drugs, and following HIV infection which causes immunodeficiency. This implies but does not conclusively prove that restraining cancer growth is part of normal immune system function. After all, transplant and HIV patients are not the same as healthy people so the data is suggestive and not proof-positive.
- Dunn, Gavin P., et al. “Cancer immunoediting: from immunosurveillance to tumor escape.” Nature immunology 3.11 (2002): 991-998.
- Burnet, Macfarlane. “Cancer—A Biological Approach: III. Viruses associated with neoplastic conditions. IV. Practical applications.” British medical journal 1.5023 (1957): 841.
- Thomas, L., and H. S. Lawrence. “Cellular and humoral aspects of the hypersensitive states.” New York: Hoeber-Harper (1959): 529-32.
- van den Broek, Maries E., et al. “Decreased tumor surveillance in perforin-deficient mice.” The Journal of experimental medicine 184.5 (1996): 1781-1790.
- Koebel, Catherine M., et al. “Adaptive immunity maintains occult cancer in an equilibrium state.” Nature 450.7171 (2007): 903-907.
- Fung, John J., et al. “De novo malignancies after liver transplantation: a major cause of late death.” Liver Transplantation 7.11B (2001): s109-s118.
- Goldstein, Daniel J., et al. “De novo solid malignancies after cardiac transplantation.” The Annals of thoracic surgery 60.6 (1995): 1783-1789.
- Curtis, Rochelle E., et al. “Solid cancers after bone marrow transplantation.” New England Journal of Medicine 336.13 (1997): 897-904.
- Kasiske, Bertram L., et al. “Cancer after kidney transplantation in the United States.” American Journal of Transplantation 4.6 (2004): 905-913.
- Euvrard, Sylvie, Jean Kanitakis, and Alain Claudy. “Skin cancers after organ transplantation.” New England Journal of Medicine 348.17 (2003): 1681-1691.
- Boshoff, Chris, and Robin Weiss. “AIDS-related malignancies.” Nature Reviews Cancer 2.5 (2002): 373-382.