Researchers at Saint Louis University School of Medicine investigated differences in T-cell responses between male and female lung cancer patients that could help guide future treatments. T-cell responses are part of the adaptive immune system, part of the body’s “smart system” that monitors threats and fights them off with personalized defenses.
“Therapies that use a patient’s immune system to fight their disease have great potential to change the way patients are treated. However, one of the biggest problems in this field right now is that these immunotherapies work well in only a small fraction of patients,” said Elise Alspach, Ph.D., assistant professor of molecular microbiology and immunology at SLU and senior author on the paper.
Alspach and his team set out to understand what determines good T cell responses in patients, why some patients seem to have better T cell responses than others, and why some patients respond well to immunotherapies. The research findings recently published in Immunological research on cancer The results show that a protein called CXCL13, which has recently been linked to immunotherapy response in patients, is expressed more in women than in men. Furthermore, Alspach and his team found that CXCL13 expression is a better marker of immunotherapy response in women than in men.
Alspach and his team used single-cell RNA sequencing on human data sets to understand more about the differences in how male and female immune systems respond to tumors. Single-cell RNA sequencing allows scientists to learn what is happening inside individual cells. Using this technology, Alspach and his team determined that T cells infiltrating female tumors are highly activated and ready to identify tumor cells and kill them. They also observed that immunosuppressive T cells are more frequently present in male tumors than in female tumors.
Alspach and her team found that there is growing evidence that male sex is associated with a better response to immunotherapy, which she says appears to contrast with their work and recently published papers showing that females develop stronger immune responses against their tumors.
“We currently do not understand why men would respond better than women to therapies targeting the immune system, but this interesting juxtaposition highlights the need for further research into the sex variable in the immune response to cancer,” Alspach said.
Alspach said the potential of immunotherapy is revolutionary as it mediates tumor rejection in patients and induces long-term remission.
“When we get infected with a virus, the immune system generates a population of cells that can remember that virus and do a better job of clearing it from the body, so the immune system does the same thing against tumors,” he said. “The memory response against that tumor partly drives the long-term remissions we see in patients treated with immunotherapies.”
Before the advent of immunotherapies, Alspach said cancer treatments were harsh on the body and not tumor-specific or, in the case of small molecule drugs that targeted specific proteins within tumor cells, often became resistant to the therapies. Today’s immunotherapies are often much better tolerated in more patients, and patients can maintain a better quality of life because the immune system can be educated to specifically attack the tumor rather than all tissues in the body.
Because immune responses against tumors are different between the sexes, Alspach and his colleagues concluded that it makes sense to design different treatments for male and female patients. In the future, he hopes that more appropriate therapeutic strategies will be designed to target the pathways that mediate better tumor control in a way that benefits individual patients.
This research was made possible by a recent investment in single-cell RNA sequencing technology at Saint Louis University, bringing researchers closer to new cures.
Other authors 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, of the Department of Molecular Microbiology and Immunology at Saint Louis University School of Medicine.