Key Immune Cells Predict Recurrence in Lung Cancer Patients
DURHAM, N.C. -- Patients treated surgically for early-stage lung cancer face an increased risk of recurrence if their tumors contain a large number of cells that act as "dimmer switches" on the immune system, according to a study at Duke University Medical Center.
These immune-suppressing cells, called T-regulatory cells, effectively turn down the action of the immune system's T-cell lymphocytes that normally fight cancer. In the study, the researchers found that the more T-regulatory cells and the fewer T-cell lymphocytes present in the tumors of treated patients, the greater the likelihood the cancer would recur.
"If further studies prove successful, it may be possible to measure the levels of T-regulatory cells in a lung cancer tumor as a marker to help predict which patients require additional chemotherapy following surgery to help prevent their cancer from recurring," said Ned Patz, M.D., senior investigator of the study and a professor of radiology, pharmacology and cancer biology.
Patz said it is essential to develop biologic markers that can help stratify patients into high-risk and low-risk categories, because the overall survival rate for early stage lung cancer patients is only 50 percent.
The findings appear online and will be published in the Dec. 15, 2006, issue of the journal Cancer. The study was funded by the National Cancer Institute.
In current practice, patients with early-stage lung cancer undergo surgery to remove their tumors, but they rarely are prescribed follow-up chemotherapy because their tumors are considered at low risk of recurrence. Yet nearly half of early stage patients will experience a recurrence of their tumors, Patz said.
There is no method of detecting which patients will recur after treatment, so physicians avoid prescribing toxic chemotherapy for the entire group of early-stage patients to prevent its harmful side effects.
In the absence of biologic markers, physicians now rely on assessing a tumor's size and location, the type types of cells it contains and whether or not it has spread to nearby lymph nodes in order to determine its stage. Yet these physical traits do not disclose the tumor's genetic composition and thus its intended course of action, just as viewing one's face or body shape cannot disclose his intent or behavior.
Thus, identifying the biologic differences between aggressive versus nonaggressive lung cancers would provide oncologists with a more accurate method of selecting the best treatments for a given patient, Patz said.
In the study, Patz' team analyzed tumor samples taken from 64 patients with early-stage lung cancer who had their tumors removed. The scientists measured the levels of T-regulatory cells and T-cell lymphocytes in each tumor, and then compared the relative levels in each tumor to the patient's eventual health outcome.
Among all the patients, the risk of recurrence increased as the number of T-regulatory cells in their tumors increased, Patz said. Patients whose tumors had the highest proportion of T-regulatory cells in relation to T-cell lymphocytes suffered a recurrence 50 percent of the time. Patients without any T-regulatory cells did not suffer recurrences.
"This finding indicates that it is important to analyze the biology of the tumor cells as well as the tumor's relationship with the immune system," Patz said. "Testing newly diagnosed lung cancer patients for their levels of T-regulatory cells may serve as one important marker for their eventual risk of recurrence."
Patz said the next step is to examine what factors cause certain tumors to carry more T-regulatory cells than others. The ultimate goal, he said, would be to devise therapies that can prevent tumors from having more T-regulatory cells than T-cell lymphocytes.