Expression of lymphocyte immunoregulatory biomarkers in bone and soft-tissue sarcomas

Publication Date

2019

Journal Title

Mod Pathol

Abstract

© 2019, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. Despite advances in our understanding of the underlying molecular drivers of sarcomas, few treatments are available with proven benefit for advanced metastatic sarcomas. Immunotherapy has value in this setting for some types of cancers, but sarcomas, with their multiplicity of rare types, have not been characterized in detail for their expression of targetable immune biomarkers. This study provides the most systematic evaluation to date of tumor-infiltrating lymphocytes and immune checkpoint biomarker expression in sarcomas. We examined by morphology and immunohistochemistry 1072 sarcoma specimens representing 22 types, in addition to 236 benign bone and soft-tissue tumors. Genomically-complex sarcoma types—those driven by mutations and/or copy-number alterations—had much higher numbers of tumor-infiltrating lymphocytes than translocation-associated sarcomas. Prior exposure to radiotherapy was associated with increased immune infiltrates. Higher lymphocytic infiltration was associated with better overall survival among the non-translocation-associated sarcomas. Expression of PD-1 and CD56 were associated with worse overall survival. LAG-3 and TIM-3, two emerging immune checkpoints, were frequently expressed in most sarcoma types. Indeed, most cases positive for PD-(L)1 coexpressed one or both of these novel biomarkers, providing a potential rationale in support for trials targeting LAG-3 and/or TIM-3 in conjunction with PD-1 inhibition.

Document Type

Article

Status

Faculty

Facility

School of Medicine

Primary Department

Hematology/Medical Oncology

PMID

31263176

DOI

10.1038/s41379-019-0312-y

For the public and Northwell Health campuses

Share

COinS