Young Female Patients Have Low Response Rates to Immunotherapy

Young and female patients have low response rates to some types of cancer immunotherapy, according to a new study published in Nature Communications.

Cancer immunotherapy helps the patient’s immune system clear away tumors on its own, according to the study. Major histocompatibility complexes (MCH) are displayed on the surface of most cells in the body as “antigen flags” to immune cell surveyors that check for damaged or infected cells, the study authors wrote.

Most are caught, but some cancerous cells throw up “stop signals” to MCHs. Immune checkpoint inhibitors work by using antibodies to make cancer cells visible to the immune system. For many, it is a promising therapy, but in others, immunotherapy doesn’t work. The group most notably affected by this are young female patients.

The study authors examined data from nearly 10,000 patients with cancer collected from the National Institutes of Health’s Cancer Genome Atlas. An additional 342 patients with other types of tumors from the International Cancer Genome Consortium database were also included, according to the press release.

Although researchers found no age- or sex-related differences in MHC function, they did find that younger women tended to amass more cancer-causing genetic mutations that MCHs can’t sort effectively. According to the study, this may be because young female patients have a robust immune system that is better equipped to get rid of well-presented mutant self-antigens while not catching tumor cells with poorly presented mutations.

"This shows an important thing, that the interplay between the cancer genome and the adaptive arm of the immune system is not a static one…Two simple but important variables, age and sex, influence this interplay. The study also emphasizes the master role of the MHC in dictating the outcome of this interplay, reaffirming its central role in the evolution of disease, cancer included, at the level of the individual and population,” said study co-author Maurizio Zanetti, MD, professor of medicine at UC San Diego School of Medicine and head of the Laboratory of Immunology at UC San Diego Moores Cancer Center, in the press release.

The researchers said that although their findings concern younger people, this does not necessarily mean children. Generally, pediatric tumors are very different from adult tumors, the study authors noted.

Reference:

Why young and female patients don't respond as well to cancer immunotherapy (news release), San Diego, CA, August 17, 2020, ScienceDaily, Accessed August 18, 2020