The Connection between Cancer & the Immune System
Cancer Research Institute 2003

In 1909, a scientist by the name of Paul Ehrlich proposed that the incidence of cancer would be much greater were it not for the vigilance of our immune defense system in identifying and eliminating nascent tumor cells. This suggestion gave birth to the generally accepted concept that the immune system plays a vital role in the identification and elimination of transformed cells. About 50 years later, two scientists, Lewis Thomas and Frank MacFarlane Burnet, took Paul Ehrlich’s original idea a step further and proposed that a special type of immune cell called a T cell was the pivotal sentinel in the immune system’s response against cancer. This elaboration led to the coinage of the term “immune surveillance or immunosurveillance” to describe the concept whereby the immune system is on perpetual alert against transformed cells.

As dictated by the scientific method, theories must in the course of time either withstand rigorous experimental testing, crumble and be discarded or be improved upon. This basic requirement brought the theory of immunosurveillance under severe attack and great controversy when scientists like Osías Stutman showed in the 1970s that mice supposedly lacking an intact immune system (so-called nude mice) did not become more susceptible to tumor growth as predicted by the theory.

Thus, the theory of immunosurveillance remained controversial until an important scientific article entitled “IFN-gamma and lymphocytes prevent primary tumor development and shape tumor immunogenicity” was published in the journal Nature on April 26, 2001. This breakthrough article was authored by Robert D. Schreiber, Ph.D., and his colleagues at Washington University School of Medicine, St. Louis, MO, in collaboration with Lloyd J. Old, M.D., of the Ludwig Institute for Cancer Research and Memorial Sloan-Kettering Cancer Center, New York, NY. The experimental evidence presented in their paper unambiguously showed that the immune system can and often does prevent tumors from developing, and thus plays a strong protective role against cancer. These researchers also uncovered important new insights regarding the immune system and tumor development that they dubbed “immunoediting.”

Utilizing genetically engineered mice that lacked a functional immune system, the authors showed that lymphocytes and the immune stimulator, IFN-gamma, cooperate to inhibit the development of both spontaneous and carcinogen-induced tumors. Unfortunately, this natural body defense is imperfect, and some tumor cells escape identification and go on to cause cancer. These renegade tumors are less immunogenic, having undergone a process of immunoselection triggered by the actions of the immune system. Conceptually, in much the same way as bacteria can become resistant to antibiotic treatment and lead to more potent and harmful strains, so too can the body’s own tumor defense system lead to tumors that escape elimination.

Importantly, these researchers went on to demonstrate that there are ways to overcome the “camouflage” of such renegade tumors by increasing their antigen expression and making them visible to the immune system. This suggests that even tumors that have escaped recognition can be turned into targets for an immune response. Further experimentation is underway to test how these results can be used to develop cancer immunotherapies. The Cancer Research Institute (CRI) sponsored this research with a grant to Dr. Schreiber’s lab and provided further funding through its pre- and post-doctoral training programs to two graduate students, one of whom was the first author of the paper, and a postdoctoral fellow.

Despite the tremendous scientific progress (such as that described above) that has been made over the years, a complete and precise understanding of the immune system’s response to cancer remains elusive. The continued exploration of these questions is the province of cancer immunology; the scientific discipline to which CRI is dedicated to supporting and nourishing.

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