Immune profiles of desmoplastic small round cell tumor and synovial sarcoma suggest different immunotherapeutic susceptibility upfront compared to relapse specimens

Pediatr Blood Cancer. 2018 Nov;65(11):e27313. doi: 10.1002/pbc.27313. Epub 2018 Jul 17.

Abstract

Background: Desmoplastic small round cell tumor (DSRCT) and synovial sarcoma are rare tumors with dismal outcomes requiring new therapeutic strategies. Immunotherapies have shown promise in several cancer types, but have not been evaluated in DSRCT and synovial sarcoma. Because the immune microenvironment can provide indications of the inflammatory nature of tumors, immunohistochemical staining is able to assess the tumor immune infiltrates in both tumor types.

Procedure: Using tissue microarrays of DSRCT and synovial sarcoma tumor samples, we detected tumoral HLA-A/B/C, beta-2-microglobulin(B2M), and PD-L1 expression, and quantified tumor-infiltrating lymphocytes expressing CD4, CD8, CD56, CD45RO, or FOXP3 by immunohistochemistry. We used staining intensity on a scale of 0-3 and percentage of tumor stained to determine HLA, B2M, and PD-L1 scores. We calculated the cytotoxic T lymphocyte (CTL) target score as HLA score × B2M score/100.

Results: In diagnostic samples, we found high HLA and CTL target scores and low PD-L1 expression with decreased scores in recurrence for both tumor types. We found an increase in CD56+ natural killer cells in DSRCT samples from diagnosis to recurrence.

Conclusions: We found similar immunostimulatory profiles in DSRCT and synovial sarcoma. Our findings suggest that DSRCT and synovial sarcoma may be amenable to immunotherapies, albeit there was significant heterogeneity. Interestingly, HLA and CTL target scores decreased at recurrence, possibly reflecting immunoevasion. Our findings suggest both tumor types may be amendable to CTL-based therapies at diagnosis but less so at relapse. Our results support further investigation into the prognostic and predictive value of these findings in a larger dataset.

Keywords: DSRCT; immune profile; immunohistochemistry; synovial sarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / immunology
  • Desmoplastic Small Round Cell Tumor / immunology*
  • Desmoplastic Small Round Cell Tumor / pathology
  • HLA Antigens / immunology
  • Humans
  • Immunophenotyping
  • Immunotherapy
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Neoplasm Recurrence, Local / immunology*
  • Neoplasm Recurrence, Local / pathology
  • Sarcoma, Synovial / immunology*
  • Sarcoma, Synovial / pathology
  • Soft Tissue Neoplasms / immunology*
  • Soft Tissue Neoplasms / pathology
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor
  • HLA Antigens