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

Dancsok, A. R., Setsu, N., Gao, D., Blay, J. Y., Thomas, D., Maki, R. G., Nielsen, T. O., Demicco, E. G. (July 2019) Expression of lymphocyte immunoregulatory biomarkers in bone and soft-tissue sarcomas. Mod Pathol, 32 (12). pp. 1662-1785. ISSN 0893-3952

DOI: 10.1038/s41379-019-0312-y


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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
diseases & disorders > cancer > drugs and therapies > Immunotherapy
diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matthew Dunn
Date: 1 July 2019
Date Deposited: 05 Aug 2019 16:07
Last Modified: 19 Dec 2019 18:04
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