AHN, Johns Hopkins Research Points Potential Way to Effective Immunotherapy Use for Esophageal Cancer Patients
Tuesday, September 5, 2017
Cell Culture and Animal Model Studies Published in Annals of Surgery Shows Immune Response Upregulation Post-Radiation Therapy
PITTSBURGH - Immunotherapy drugs such as nivolumab (Opdivo) have given new hope to lung cancer and melanoma patients, some of whom are seeing remarkable response rates with the new therapies. However, progress has been slow for other cancers, including one of the deadliest, esophageal cancer.
Now, in research just published in Annals of Surgery, cancer specialists at Allegheny Health Network’s Esophageal and Lung Institute and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins have looked at how the immune microenvironment changes during standard chemotherapy and radiation treatment in tissue samples from 31 esophageal cancer patients and a rat model of the disease to shed light on how immunotherapy drugs like nivolumab may help patients with esophageal cancer.
“As physicians who care for patients with esophageal cancer, we are continually working to find new ways to prevent and treat this aggressive cancer,” said Blair Jobe, MD, Chair of the Esophageal and Lung Institute at Allegheny Health Network and one of the principal investigators in the study. “We believe our findings could have significant implications for the treatment of esophageal cancer patients.”
Dr. Jobe and Ali Zaidi, MD, Director of Research at AHN’s Esophageal and Lung Institute, led the research along with Ronan Kelly, MD, MBA, associate professor at the Johns Hopkins Kimmel Cancer Center. Other AHN researchers included E. Day Werts, PhD., radiation biologist, Division of Radiation Oncology, and Jan Silverman, MD, Chair of Pathology at AHN.
Among tissue samples of esophageal cancer patients treated with combined chemotherapy and radiation, the scientists report statistically significant increases of between nearly 20 and 30 percent of the expression of proteins such as PD-L1 and CTLA-4, which are involved in regulating tumor responses to immune system cells. They also found an increase in the number of T-cells, the soldiers of the immune system, within tumor tissue samples after the patients were treated with chemo and radiation, compared with before their treatment.
In a study of 22 rats which are bred to develop acid reflux disease and subsequent esophageal cancers, the scientists treated 10 of the rats with nine weeks of a lower dose of radiation and 12 rats with a higher dose. Among the esophageal tumors removed from the rats, the scientists found up to twice the levels of PD-L1 expression the within the tumors treated with higher doses of radiation than those that received lower doses. However, because of the small sample size of rats, the changes in protein expression levels was not considered statistically significant. What the scientists did find, though, was that the expression levels were highest immediately after radiation treatment and leveled off as time went on.
“If we continue to find that radiation causes immunologic changes in tumors, we can test whether drugs that target the immune system are able to drive more cancer-killing T-cells into the tumor,” said Dr. Kelly.
The investigators hope that the human body’s dormant immune defenses can be tricked into recognizing and killing esophageal cancer cells when combined with chemo-radiation.
"Esophageal cancer is a deadly disease that even when detected early is fatal in the majority of patients. Chances of spreading throughout the body are extremely high even in patients where it is diagnosed early and resected. Therefore, newer ways are required to treat this deadly disease in real-time," said Dr. Zaidi.
The scientists at AHN and Johns Hopkins are conducting a clinical trial to test the safety and effectiveness of adding immunotherapy to standard chemotherapy and radiation in patients with esophageal cancer.
“This research is a great example of how the AHN-Johns Hopkins collaboration is benefiting patients in Pittsburgh and nationwide, combining the expertise of these two great institutions in order to advance clinical cancer care,” said David Parda, MD, Chairman, AHN Cancer Institute. “We expect many more vital collaborations as our partnership continues to grow over the coming years.”