Genetic analysis may predict which sarcoma subtypes will respond to checkpoint inhibition, according to an article published in Cancer.1

Sarcoma, although ostensibly rare, are associated with a low median survival of about 12 to 18 months. The particular subtype and degree of genetic heterogeneity could predict whether immunotherapy via PD-1, PD-L1, or CTLA-4 inhibition would be effective for patients with sarcoma, a disease with “unique and diverse biologic features.”

For this study, researchers evaluated genetic expression among tumors from 81 patients with sarcoma; immunohistochemistry for PD-1/PD-L1 and T cell receptor V-beta gene sequencing were also performed.

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The included sarcoma subtypes were liposarcoma (27), leiomyosarcoma (19), pleomorphic (20), and synovial sarcoma (15).

Undifferentiated pleomorphic sarcomas had the genetic expression most associated with T cell infiltration, as well as higher levels of PD-L1, PD-1, and T cell infiltration. Synovial sarcoma samples had the lowest T cell infiltration.

High T cell infiltration and clonality were directly linked to high PD-1/PD-L1 expression.

The authors noted that “inflamed” sarcomas — due to chemotherapy, radiotherapy, or others factors — may be more likely to respond to checkpoint inhibition.

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They concluded that immune profiling may effective guide immunotherapy-based treatment in this disease setting. Clinical trials evaluating for genetic expression among sarcomas to guide checkpoint inhibition are warranted.


  1. Pollack SM, He Q, Yearley JH, et al. T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. Cancer. 2017 May 2. doi: 10.1002/cncr.30726 [Epub ahead of print]