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
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.
| Item Type: |
Paper
|
| Subjects: |
bioinformatics
diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
Investigative techniques and equipment
diseases & disorders > neoplasms
Investigative techniques and equipment > biomarker
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
diseases & disorders > cancer > drugs and therapies
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
diseases & disorders > cancer > drugs and therapies > Immunotherapy
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte
organs, tissues, organelles, cell types and functions
diseases & disorders > cancer > cancer types > sarcoma
diseases & disorders > cancer > cancer types |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Maki lab |
| Depositing User: |
Matthew Dunn
|
| Date: |
1 July 2019 |
| Date Deposited: |
05 Aug 2019 16:07 |
| Last Modified: |
01 Feb 2024 21:15 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/38148 |
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