Scientists at Saint Louis University School of Medicine explored the differences in T-cell responses between male and female lung cancer patients, findings that could influence future treatments. T-cell responses are an integral part of the adaptive immune system, often referred to as the body’s “smart system,” which actively detects threats and combats them with tailored defenses.
“Therapies utilizing the patient’s immune system to combat their illness have significant potential to transform patient care. However, one of the major challenges currently faced is that these immunotherapies are effective only for a small percentage of patients,” stated Elise Alspach, Ph.D., an assistant professor of molecular microbiology and immunology at SLU and the paper’s senior author.
Alspach and her research team sought to uncover what factors contribute to effective T-cell responses among patients, why some individuals exhibit superior T-cell activity than others, and why certain patients respond favorably to immunotherapies. Their recent study, published in Cancer Immunology Research, revealed that a protein known as CXCL13, which has been connected to the success of immunotherapy, is expressed at higher levels in females compared to males. Furthermore, they found that CXCL13 is a more reliable indicator of immunotherapy response in female patients than in male patients.
Employing single-cell RNA sequencing techniques on human datasets, Alspach and her team sought to delve deeper into the variations in immune responses between male and female patients with tumors. This innovative technology enables scientists to observe the internal workings of individual cells. Through this approach, they discovered that T-cells in female tumors are markedly activated and primed to detect and destroy tumor cells, while immune-suppressive T-cells were more common in male tumors compared to their female counterparts.
Alspach and her colleagues observed emerging evidence suggesting that males might fare better with immunotherapy, a finding that seemingly contradicts their results and other recent studies showing that females exhibit stronger immune responses against their cancers.
“At present, we do not fully grasp why males might have a superior response to immune-targeting therapies, but this intriguing contrast underscores the necessity for further investigation regarding the influence of sex on immune responses to cancer,” Alspach elaborated.
She emphasized the transformative potential of immunotherapy, as it facilitates tumor rejection in patients and can lead to prolonged remission times.
“When we are infected by a virus, the immune system produces a group of cells that can remember that virus and enhance its elimination from the body; similarly, the immune system responds to tumors,” she explained. “This memory response against tumors partly accounts for the long-term remissions seen in immunotherapy-treated patients.”
Prior to immunotherapy, Alspach noted that cancer treatments were often tough on the body, typically lacking specificity for tumors, and small molecule drugs targeting specific proteins within tumor cells frequently led to treatment resistance. Current immunotherapies are generally better tolerated, and patients can enjoy an enhanced quality of life since the immune system can be trained to target tumors specifically as opposed to affecting all tissues in the body.
Considering the differences in immune responses against tumors between sexes, Alspach and her colleagues suggested that it is reasonable to develop tailored treatments for male and female patients. She hopes that future strategies will emerge that target the pathways responsible for improved tumor control, customized to benefit individual patients.
This research was made feasible by a recent investment in single-cell RNA sequencing technology at Saint Louis University, bringing us closer to potential new cures.
Additional contributors to this study include Richard J. DiPaolo, Ph.D.; Ryan M. Teague, Ph.D.; Michelle Brennan, Ph.D.; David DeBruin; Chinye Nwokolo; Katey S. Hunt; Alexander Piening; Maureen J. Donlin; and Stephen T. Ferris from the Department of Molecular Microbiology and Immunology at Saint Louis University School of Medicine.
