Researchers at La Jolla Institute for Allergy and Immunology think they now may know, in part, why immunotherapy does not work for some cancer patients. In a recent issue of Nature Immunology, they report on a subpopulation of T cells in tumors known as tissue-resident memory T cells as an important distinguishing factor in cancer patients whose immune system mounts an effective anti-tumor response. The investigators recently completed a large-scale profile of gene expression patterns of cytotoxic T cells (CTLs) isolated directly from patients’ tumors and found that measuring tissue-resident memory T cells is a potential way of judging tumor immune fitness.
The researchers suggest that by systematically studying cancer patients’ immune cells it may be possible to guide therapeutic decisions. They contend that this new approach, if validated, could become a new type of baseline test to predict whether a patient will respond to a specific immunotherapy.
“We found that presence of a type of T cell—called tissue-resident memory cell—in the tumor tissue is associated with good outcomes in cancer,” said study investigator Pandurangan Vijayanand, MD, PhD, an associate professor at the La Jolla Institute, La Jolla, California.
Vijayanand and colleagues compared gene expression profiles of CTLs isolated from 41 head and neck tumors and 36 untreated, early-stage lung tumors with CTLs isolated from adjacent normal lung tissue. They identified a shared molecular fingerprint between different tumor types suggesting extensive reprogramming of CTLs infiltrating tumor tissue.
Beyond their shared molecular signature, tumor-infiltrating CTLs differed widely in their expression of molecules associated with T-cell activation and known immune checkpoints. Gene expression patterns that signal the presence of tissue-resident memory T cells corresponded with better anti-tumor activity. A large-scale analysis in an independent cohort of 689 lung cancer patients confirmed that patients with a high density of tissue-resident memory T cells in tumor tissue survived significantly longer, demonstrating that these cells serve a critical role in protecting against tumor recurrence.
“Profiling tumor immune cells by RNA-Seq yields rich information that may be used for rationalizing choice of immunotherapy for cancer patients,” Dr. Vijayanand told OncoTherapy Network. “We are testing the value of this approach in predicting clinical responders enrolled in prospective clinical trials of new immunotherapy agents.”
It is believed that some patients fail immunotherapy because of inhibitory molecular signals emitted from a tumor or its environment undercutting the immune response. First author on the study, Anusha-Preethi Ganesan, MD, PhD, from the division of pediatric hematology and oncology at Rady’s Children’s Hospital, UC San Diego, said if immunotherapies are based on activating T cells to kill tumor cells it is important to know the transcriptional profiles of the T cells and what molecules they make.