Tumors Attacked By Immune System Respond Better To
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
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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