Tumors Attacked By Immune System Respond Better To Therapy

(Philadelphia, PA) - The presence of tumor-infiltrating lymphocytes predicts the length of remission after chemotherapy and the overall survival of patients with ovarian cancer, according to researchers from the Abramson Cancer Center and the Center on Women's Health at the University of Pennsylvania School of Medicine. Their findings, which are presented in the January 16th issue of the New England Journal of Medicine, constitute the first proof that a spontaneous immune response against the tumor dramatically impacts the clinical course of ovarian cancer. These novel findings generate hope that immune therapies may significantly prolong the response to chemotherapy and improve the survival of patients with advanced ovarian carcinoma.

Each year, epithelial ovarian cancer - the most frequent cause of death from gynecological cancer - accounts for approximately 14,000 deaths in the United States. Frequently, the disease is not caught until it is already at an advanced stage and, despite the use of surgery and chemotherapy, the overall survival rate after five years remains at 25%.

"The patient's immune response to ovarian cancer is one of the strongest predictors of outcome after completion of chemotherapy. Our findings show that the five-year survival rate of patients whose tumors were infiltrated by lymphocytes was 38%, as compared to 4.5% for patients whose tumors lacked these lymphocytes" said George Coukos, MD, PhD, assistant professor in Penn's Department of Obstetrics and Gynecology and director of Gynecologic Malignancy Research Programs. "In fact, only patients with these tumor-infiltrating lymphocytes survived beyond 5 years. Moreover, a subset of patients who had optical surgical resection of their tumor, had complete response to chemotherapy and showed evidence of antitumor immune response, experienced up to 70% survival at ten years, a remarkable rate of survival for advanced ovarian cancer."

Although these findings are extraordinarily optimistic, Coukos and his colleagues caution that larger scale studies are necessary to validate these observations. "It is clearly a step forward in understanding how to treat this disease. Meanwhile, our findings tell us that we need to identify proper ways to boost patients' immune response against tumors," said Coukos. "While activated lymphocytes greatly increases a patient's chances, it is clear that the immune system needs help. This is added incentive to explore the use of vaccines against tumors and other means to induce or enhance an immune response."

Tumor vaccines use the patient's own tumor tissue to create a customized vaccine against the growing cancer. Current research into tumor vaccines has met with promising clinical and scientific results.

In addition, now that we know that there are two types of patients with respect to antitumor immune response, a lot of work remains to be done to identify the most appropriate chemotherapy for each type. Ironically, some of the most effective chemotherapeutics suppress the immune system.

"The challenges of the future include understanding why specific patients mount an antitumor immune response, while others don't, and how we can induce potent antitumor immune response in all patients," said Coukos. "We also need to design more rational treatments combining surgery, appropriate chemotherapy and efficient immune therapy in ways that are tailor-made for an individual patient."

This research was supported by grants from the American Association of Obstetricians and Gynecologists Foundations, the Gynecological Cancer Foundation, the National Cancer Institute and the Abramson Family Cancer Research Institute.

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