Expression of programmed death-ligand 1 (PD-L1) in immune cells and immature stromal differentiation are associated with worse cancer-free survival in patients with gastrointestinal stromal tumors (GISTs), according to a new study published in the journal Pathology – Research and Practice.

Positive expression of a protein called v-domain Ig suppressor of T cell activation (VISTA) is also associated with better outcomes. These findings support the evaluation of stromal differentiation and PD-L1 and VISTA expression in patients with GISTs.

“Ultimately, we hope our findings lead to improved prognostication, further optimization of therapeutics, and improved outcomes in a true clinical environment,” the researchers wrote.

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Previous research has shown immature stroma to be associated with poor prognosis in many types of cancer such as cancers of the colon, breast, cervix, esophagus, and stomach. However, its relevance in GIST has not been explored. Similarly, immune checkpoint inhibition has been shown to be associated with worse outcomes in many cancers. 

Read more about GIST prognosis

Here, a team of researchers led by Mansoor Nasim, MD, PhD, used specimens collected from 105 patients diagnosed with GISTs at the Northshore University and Long Island Jewish Hospitals in New York between 2010 to 2017.

The team assessed stromal differentiation as well as PDL-1 and VISTA expression in the specimens. They also collected cancer-free survival data for all patients with a mean follow-up time of 5.2 years. 

Statistical analyses revealed that high-grade immature stromal differentiation had the highest tendency for recurrence or death. It was the only variable with a prognostic significance.

“Our findings support the evaluation of [stromal differentiation], PD-L1 and VISTA in GIST, with clinical practice implications for pathologists,” the researchers wrote. “PD-L1 and VISTA could be both clinically relevant and targetable, while [stromal differentiation] may be the answer to clinical heterogeneity.”


Hacking S, Wu D, Lee L, Vitkovski T, Nasim M. Nature and significance of stromal differentiation, PD-L1, and VISTA in GIST. Pathol Res Pract. Published online November 24, 2021. doi:10.1016/j.prp.2021.153703