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Navigating immune suppression: the convergence of transplant and cancer biology

OCTOBER 22, 2018
Clinical Congress Daily Highlights, Monday First Edition


Successful transplantation is an incredible feat of modern medicine, with lifesaving outcomes across many clinical contexts. In Monday’s I. S. Ravdin Lecture in the Basic and Surgical Sciences, John Julian Fung, MD, PhD, FACS, FAASLD, Transplantation Institute, University of Chicago Medical Center, discussed how far we’ve come.

As early as the 1940s, surgeons used allogeneic skin as a temporary “dressing” for burns. The next two decades witnessed the first successful kidney transplant and nonautologous bone marrow transplant. However, both were successful because identical twin donors were available.

The next wave of innovation relied on addressing immune compatibility in new ways. Identification and ability to match the major histocompatibility complex (MHC) between donor and host, and the use of steroids to initiate nonmatching transplants, were important advances in improving transplant outcomes.

In recent years, research has focused on characterizing the various cell types and cellular activities that promote successful transplantation. A better understanding of immunosuppression, regulated by T-cells and other innate modulators of immune activity, has paved the way for the development of many new immunosuppressive drugs that have contributed to a gradual decrease in transplantation rejection rates.

Dr. Fung presented work on the factors affecting allogeneic transplant, particularly in the liver, focusing on the role of hepatic stellate cells. The liver has unique abilities to modulate the immune response, and its tolerogenic properties may be related to its role as the interface between the gut and the blood. Dr. Fung presented data demonstrating that hepatic stellate cells appear to modulate T cell activity directly through PD-L1 apoptosis, but may also influence other cell types that exert immunosuppressive functions.

Unfortunately, there is another side of immunosuppression associated with undesirable outcomes. By nature, cancer cells evade immune surveillance, taking advantage of many of the same processes that transplant surgeons do. Dr. Fung noted that the similarities between the tolerant state and cancer so striking that he is optimistic these once disparate fields can inform each other: “Checkpoint and immune modulation, and now therapy for cancer, would have been hard to predict ten years ago, and we are now at a convergence point in our understanding of cancer immune biology and transplant immune biology.”

Additional Information

The Named Lecture, I.S. Ravdin Lecture in the Basic and Surgical Sciences, was held October 22 at the 2018 Clinical Congress of the American College of Surgeons in Boston, MA. Program, webcast, and audio information is available online at facs.org/clincon2018.

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