Expression of Programmed Cell Death Proteins in Kaposi Sarcoma and Cutaneous Angiosarcoma

J Immunother. 2020 Jun;43(5):169-174. doi: 10.1097/CJI.0000000000000317.

Abstract

Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory patients with classic Kaposi sarcoma (CKS) and human immunodeficiency virus (HIV)-associated Kaposi sarcoma (HIV-KS) there is a high need for more effective treatment modalities. The aim of this work was to study programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) protein expression and related immune parameters in CKS, HIV-KS, and CAS and correlate it with other immunologic parameters and clinical data. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tumor tissue of 19 CKS, 7 HIV-KS, and 12 CAS patients using antibodies against the following (and they are): PD-1, PD-L1, CD4, CD8, CD56, and FOXP3. PD-1 expression significantly correlated with PD-L1 expression Moreover, PD-1 and PD-L1 expression significantly correlated with CD56 and FOXP3 expression. High intratumoral FOXP3 expression was significantly associated with disease relapse (P=0.029). CD4 and FOXP3 expression was significantly higher in CKS and CAS, as compared with HIV-KS. All in all, PD-1 and PD-L1 expression was relatively weak and did not significantly differ between CKS, HIV-KS, and CAS patients. Nevertheless, PD-1 was positive in 31.6% of CKS, 28.6% of HIV-KS, and 33.3% of CAS patients. PD-L1 was expressed in 36.6% of CKS, 28.6% of HIV-KS, and 41.7% of CAS patients. We have provided evidence that PD-1/PD-L1 signalling is of importance in angiosarcomas such as CKS, HIV-KS, and CAS. Our results support the notion that the use of PD-1/PD-L1 inhibitors may represent an effective strategy against these tumors.

MeSH terms

  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Biomarkers, Tumor
  • Gene Expression*
  • Hemangiosarcoma / diagnosis
  • Hemangiosarcoma / genetics*
  • Hemangiosarcoma / metabolism
  • Hemangiosarcoma / therapy
  • Humans
  • Immunohistochemistry
  • Lymphocyte Count
  • Prognosis
  • Sarcoma, Kaposi / diagnosis
  • Sarcoma, Kaposi / genetics*
  • Sarcoma, Kaposi / metabolism
  • Sarcoma, Kaposi / therapy
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor