PD-1, PD-L1, IDO, CD70 and microsatellite instability as potential targets to prevent immune evasion in sarcomas

Immunotherapy. 2023 Oct;15(15):1257-1273. doi: 10.2217/imt-2022-0049. Epub 2023 Sep 4.

Abstract

Background: Soft tissue and bone sarcomas are rare entities, hence, standardized therapeutic strategies are difficult to assess. Materials & methods: Immunohistochemistry was performed on 68 sarcoma samples to assess the expression of PD-1, PD-L1, IDO and CD70 in different tumor compartments and molecular analysis was performed to assess microsatellite instability status. Results: PD-1/PD-L1, IDO and CD70 pathways are at play in the immune evasion of sarcomas in general. Soft tissue sarcomas more often show an inflamed phenotype compared with bone sarcomas. Specific histologic sarcoma types show high expression levels of different markers. Finally, this is the first presentation of a microsatellite instability-high Kaposi sarcoma. Discussion/conclusion: Immune evasion occurs in sarcomas. Specific histologic types might benefit from immunotherapy, for which further investigation is needed.

Keywords: CD70; IDO; MSI; PD-1; PD-L1; immune checkpoint; immunotherapy; microsatellite instability; sarcoma; tumor microenvironment.

Plain language summary

Sarcomas of the soft tissue and bone are rare cancers. When these cancers spread to other parts of the body, it is hard to find good treatments. Recently, doctors have been using a new type of treatment called immunotherapy to fight several types of cancer. Immunotherapy works by getting one's body's own defense cells to attack the cancer cells. Unfortunately, immunotherapy does not work well for sarcomas and we do not know why. This study was designed to determine if there are certain mechanisms in these tumors that help the cancer cells to hide from defense cells. Determining how to change these mechanisms could make immunotherapy a better treatment for sarcomas in the future.

MeSH terms

  • B7-H1 Antigen / genetics
  • Bone Neoplasms*
  • CD27 Ligand
  • Humans
  • Immune Evasion
  • Microsatellite Instability
  • Osteosarcoma*
  • Programmed Cell Death 1 Receptor
  • Sarcoma* / genetics
  • Sarcoma* / therapy
  • Soft Tissue Neoplasms*

Substances

  • Programmed Cell Death 1 Receptor
  • B7-H1 Antigen
  • CD70 protein, human
  • CD27 Ligand