Immune profiles of desmoplastic small round cell tumor and synovial sarcoma suggest different immunotherapeutic

Mary Frances Wedekind1,2, Kellie B Haworth3, Michael Arnold4,5

  • 1Division of Hematology, Oncology, Blood and Marrow Transplant, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio.

Abstract

Insights

Desmoplastic small round cell tumors (DSRCT) and synovial sarcoma show similar immune profiles, suggesting potential for immunotherapy. However, immune evasion may occur at recurrence, impacting treatment effectiveness.

Area of Science:

  • Oncology
  • Immunology
  • Pathology

Background:

  • Desmoplastic small round cell tumor (DSRCT) and synovial sarcoma are rare cancers with poor prognoses.
  • New therapeutic strategies, including immunotherapy, are needed for these tumors.
  • The tumor immune microenvironment, assessed by immunohistochemistry, can indicate tumor inflammation and guide treatment strategies.

Purpose of the Study:

  • To evaluate the potential of DSRCT and synovial sarcoma for immunotherapy.
  • To assess tumor immune infiltrates and expression of immune markers in DSRCT and synovial sarcoma.
  • To investigate changes in immune profiles from diagnosis to recurrence.

Main Methods:

  • Tissue microarrays of DSRCT and synovial sarcoma samples were analyzed.
  • Immunohistochemistry was used to detect tumoral HLA-A/B/C, beta-2-microglobulin (B2M), and PD-L1 expression.
  • Tumor-infiltrating lymphocytes (CD4, CD8, CD56, CD45RO, FOXP3) and cytotoxic T lymphocyte (CTL) target scores were quantified.

Main Results:

  • Both DSRCT and synovial sarcoma exhibited high HLA and CTL target scores with low PD-L1 expression at diagnosis.
  • Scores for HLA and CTL targets decreased at recurrence, suggesting immunoevasion.
  • An increase in CD56+ natural killer cells was observed in DSRCT from diagnosis to recurrence.

Conclusions:

  • DSRCT and synovial sarcoma share similar immunostimulatory profiles, indicating potential amenability to immunotherapy.
  • Heterogeneity exists within these tumor types, potentially impacting treatment response.
  • CTL-based therapies may be more effective at diagnosis than at relapse due to immunoevasion.

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