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Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma

Summary of work

A team led by PICI Scientific Steering Committee member Nir Hacohen, PhD, at Massachusetts General Hospital, found a new potential biomarker for response to immunotherapy treatment. Using single cell sequencing, researchers identified clusters of T-cells associated with response or lack of response to checkpoint inhibitors, the most commonly used form of immunotherapy. Among the cluster of T-cells linked to cancer regression after treatment, they found the expression of the transcription factor TCF7 was higher and linked to positive outcomes in patients. The team demonstrated how an immunofluorescence assay could be used to measure TCF7 in a clinical setting with patient samples, showing an association with effective therapy. Jennifer Wargo, MD, a PICI investigator at MD Anderson Cancer Center, is a co-author.

Why this is impactful to patients

To make checkpoint inhibitors work for more patients and more types of cancer, scientists have been searching for biomarkers that will help predict which people will respond successfully to these drugs. This paper provides the first evidence that TCF7, a master regulator of T-cell development that is important for generating an immune response against cancer, could be an important new immunotherapy biomarker worthy of additional investigation, said Daniel Wells, PhD, PICI senior data scientist. “They not only discovered what appears to be an important new biomarker, but also that it could be useful in the clinic sooner rather than later using a common assay, which would be of great benefit to patients,” Wells said.