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

Amanda R. Dancsok, Nokitaka Setsu, Dongxia Gao, Jean Yves Blay, David Thomas, Robert G. Maki, Torsten O. Nielsen, Elizabeth G. Demicco

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalModern Pathology
DOIs
Publication statusPublished - Jan 1 2019

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Sarcoma
Biomarkers
Lymphocytes
Bone and Bones
Tumor-Infiltrating Lymphocytes
Immunotherapy
Neoplasms
Radiotherapy
Immunohistochemistry
Mutation

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Expression of lymphocyte immunoregulatory biomarkers in bone and soft-tissue sarcomas. / Dancsok, Amanda R.; Setsu, Nokitaka; Gao, Dongxia; Blay, Jean Yves; Thomas, David; Maki, Robert G.; Nielsen, Torsten O.; Demicco, Elizabeth G.

In: Modern Pathology, 01.01.2019.

Research output: Contribution to journalArticle

Dancsok, Amanda R. ; Setsu, Nokitaka ; Gao, Dongxia ; Blay, Jean Yves ; Thomas, David ; Maki, Robert G. ; Nielsen, Torsten O. ; Demicco, Elizabeth G. / Expression of lymphocyte immunoregulatory biomarkers in bone and soft-tissue sarcomas. In: Modern Pathology. 2019.
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