Investigators have discovered that a certain type of immune cell in tumors, known as tissue-resident memory cells, are associated with a strong immune response and improved prognosis in lung cancer. The findings may aid in selecting appropriate immunotherapies and developing more effective vaccines for a wide range of cancers.

Investigators have discovered that the presence of a certain type of immune cell in tumors may be a biomarker of response to immunotherapy. The findings may help oncologists predict which patients are most likely to benefit from checkpoint inhibitors and potentially aid in developing more effective cancer vaccines.

The researchers analyzed immune cells in the tumors of patients with lung cancer who hadn't yet been treated and found an association between better outcomes and higher density of a subpopulation of tumor-fighting CD8 T cells known as tissue-resident memory (TRM) cells. The finding may explain, in part, why many patients do not respond to immunotherapy regardless of the density of CD8 T cells in their tumors (Nat Immunol 2017;18:940–50).

“When we looked at the T-cell gene expression profile of tumors with good versus bad outcomes, one thing that stood out was the TRM signature,” says study co-author Pandurangan Vijayanand, MD, PhD, associate professor at the La Jolla Institute for Allergy & Immunology in California. “Having a high number of TRM cells in their tumors tends to put patients at a very low risk of dying or having recurrence.”

TRM cells are already known to play a critical role in fighting infection in the lungs and are known to play an important role in promoting the effectiveness of influenza vaccines, notes Jonathan Powell, MD, PhD, professor of oncology at Johns Hopkins Medicine and associate director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy in Baltimore, MD. However, before this study very little was known about their role in cancer.

“It was surprising to learn that TRM cells in tumors represent a powerful marker for a positive prognosis,” he says. “These findings have the potential to help us predict which patients will respond to checkpoint blockade. They also suggest that efforts to develop new vaccines should be focused on generating these types of antitumor cells.”

The results also suggest that analyzing the composition of T cells in patients' tumors should become a routine part of clinical trials and cancer treatment, says Vijayanand. Transcriptional profiling of patients' immune cells both pre- and post-treatment could provide a rationale for selecting appropriate immunotherapies and assessing patients' responses as treatment progresses.

The strategy used in this study—purifying relevant immune-cell populations from relatively small tissue samples and performing RNA sequencing to generate genome-wide transcriptional data—can be applied to any accessible tumor type, notes Vijayanand. The approach could become a standard method of identifying biomarkers of response to immunotherapy and aid in discovering novel drug targets.

“In addition to sending tumor tissue for genome sequencing or standard pathology analysis following a resection or biopsy, efforts should be taken in characterizing the immune cells that are present in tumors,” he says. “Building that into any clinical trial or treatment program is essential to move forward because we now know that TRM cells are directly influencing outcomes.” –Janet Colwell

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