Immune Response

Inaugural Evergrande Symposium explores chronic inflammation in multiple diseases

Inflammatory diseases are rising to epidemic levels. Diagnoses of inflammatory bowel disease, for example, have soared six-fold over the past 30 years, and food allergies have doubled in half that time.

These sobering statistics come from the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women’s Hospital. The center was established in 2013 to investigate the chronic inflammation underlying autoimmune, neurological and metabolic diseases, as well as environmental factors that may influence them.

Evergrande Center symposium speakers (from left) Ana Anderson, Fiona Powrie and Lawrence Steinman; organizers Vijay Kuchroo and Arlene Sharpe; speakers Ruslan Medzhitov, Bruce Walker and Diane Mathis. Image: Suzanne Camarata Photography

The first Evergrande Center Symposium, held on Aug. 1, was designed to highlight progress, encourage collaboration and accelerate both basic and translational research.

The symposium, “Immunity and Inflammation in Disease and Tissue,” drew experts from around the world and an audience that overflowed the Rotunda meeting room in the Joseph B. Martin Conference Center.

The meeting was organized by Vijay Kuchroo, the HMS Samuel L. Wasserstrom Professor of Neurology at Brigham and Women’s and director of the Evergrande Center, and Arlene Sharpe, HMS George Fabyan Professor of Comparative Pathology and co-director of the Evergrande Center.

Speakers listen to Ruslan Medzhitov discuss inflammation and homeostasis. Image: Suzanne Camarata PhotographyRuslan Medzhitov, the David W. Wallace Professor of Immunobiology at Yale University School of Medicine, discussed inflammation and homeostasis in terms of systems dynamics and control theory rather than from only a pathological perspective.

Ana Anderson, HMS assistant professor of neurology at Brigham and Women’s, described her work with Tim-3, a key regulator of T cell dysfunction in cancer. This checkpoint on the cell surface is turned off in cancer, disabling the proper immune response to tumor cells it encounters.

Two other checkpoints, called CTLA4 and PD-1, are the subject of intense research efforts at HMS, she said. They are the targets of antibodies that take the brakes off the immune cells so the cells can combat cancer. An approved anti-CTLA4 drug for melanoma is successful in 10 to 15 percent of patients, while anti-PD-1 drugs in clinical trials have helped 28 to 52 percent of melanoma patients, she said. There have been different degrees of success in other cancers.

“We are getting responses, but we can do better,” Anderson said, suggesting a combination strategy targeting both Tim-3 and PD-1.

Lawrence Steinman, professor of neurology and neurological sciences and pediatrics at Stanford University, talked about antigen-specific therapy and its challenges. Using DNA vaccines, he has developed two antigen-specific therapies for multiple sclerosis and type 1 diabetes.

The challenge is creating therapies that silence inappropriate immune responses without disabling the proper function of the immune system, he said.

“Maybe in the lifetime of some of the people in this room, somebody will do something like Salk and Sabin did for polio,” he said.

Diane Mathis, the Morton Grove-Rasmussen Chair in Immunohematology at HMS, discussed T cell players in organismal metabolism. These immune cells are major regulators of autoimmune, allergic, infectious and antitumor responses.

Her work explores why regulatory T cells are lost in obesity, leading to insulin resistance and other metabolic problems.

“One of the morals of the story is, regulatory T cells can control critical, non-immune processes,” she said.

Ana Anderson (at podium, right) answers a question from Bruce Walker. Image: Suzanne Camarata Photography

Bruce Walker, HMS professor of medicine at Massachusetts General Hospital and director of the Ragon Institute of MGH, MIT and Harvard, called the HIV epidemic the “signature global health problem of our generation.”

While noting that remarkable gains in treatment have been made, he also asserted the urgent need for a vaccine, given the high rate of treatment failure among young people in Africa.

Walker described a research project in South Africa called Females Rising through Education, Support and Health (FRESH). Designed to investigate the earliest stages of infection among young women in the country, it also doubles as an educational effort to help reduce the likelihood of infection through improving economic health.

“There is an urgent need for a vaccine that does better,” he said.

Fiona Powrie, the Sidney Truelove Professor of Gastroenterology at the University of Oxford, discussed immune pathways in the intestine in health and disease, charting the interplay between hosts and microbes.

Chronic inflammation arises when that dialogue breaks down, she said, acknowledging that Crohn’s disease and ulcerative colitis are complex diseases that arise from many factors.