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Predicting Which Melanoma Tumors Will Respond to Checkpoint Immunotherapy

By: Anna Nowogrodzki
Posted: Monday, January 28, 2019

Certain gene expression markers in CD8 T cells may help to distinguish between patients’ melanoma tumors that respond to checkpoint immunotherapy and those that do not respond, according to a study of immune cell transcriptomes. Blocking the genes CD39 and TIM3 in mice with melanoma increased survival and decreased tumor size. The study was published in Cell by co-senior authors Nir Hacohen, PhD, and Gad Getz, PhD, of Massachusetts General Hospital and the Broad Institute of Harvard and MIT, and colleagues.

“As checkpoint inhibition becomes the standard of care for tens and thousands of patients worldwide, there is an unmet need to apply the strategy used in this study to other types of cancer to discover the specific mechanisms underlying the success or failure of this type of treatment,” stated Dr. Getz in a Broad Institute press release.

The investigators studied 48 tumors (17 responsive to treatment, 31 unresponsive) from 32 patients treated with checkpoint inhibitors. The authors sequenced the immune cells in each tumor using single-cell RNA sequencing. The 48 tumors contained more than 16,000 immune cells.

Expression of the transcription factor TCF7 and lack of expression of the genes CD39 and TIM3 were markers of responsive tumors, whereas expression of the transcription factor BATF was a marker of unresponsive tumors. The authors developed a staining test to distinguish responsive and unresponsive tumors by measuring levels of TCF7 in CD8 T cells.

Mice with melanoma had smaller tumors and longer 40-day survival when the authors blocked the genes CD39 and TIM3 at the same time. Blocking CD39 while also using a checkpoint inhibitor (PD-1 or PD-1/CTLA-4) yielded a 3-fold increase in 40-day survival.

Disclosure: The study authors’ disclosure information may be found at cell.com.



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