CD70 and PD-L1 (CD274) co-expression predicts poor clinical outcomes in patients with pleural mesothelioma

J Pathol Clin Res. 2023 May;9(3):195-207. doi: 10.1002/cjp2.310. Epub 2023 Feb 8.


Diffuse pleural mesothelioma (PM) is a highly aggressive tumour typically associated with short survival. Recently, the effectiveness of first-line immune checkpoint inhibitors in patients with unresectable PM was reported. CD70-CD27 signalling plays a co-stimulatory role in promoting T cell expansion and differentiation through the nuclear factor κB (NF-κB) pathway. Conversely, the PD-L1 (CD274)-PD-1 (PDCD1) pathway is crucial for the modulation of immune responses in normal conditions. Nevertheless, pathological activation of both the CD70-CD27 and PD-L1-PD-1 pathways by aberrantly expressed CD70 and PD-L1 participates in the immune evasion of tumour cells. In this study, 171 well-characterised PMs including epithelioid (n = 144), biphasic (n = 15), and sarcomatoid (n = 12) histotypes were evaluated immunohistochemically for CD70, PD-L1, and immune cell markers such as CD3, CD4, CD8, CD56, PD-1, FOXP3, CD68, and CD163. Eight percent (14/171) of mesotheliomas simultaneously expressed CD70 and PD-L1 on the tumour cell membrane. PMs co-expressing CD70 and PD-L1 contained significantly higher numbers of CD8+ (p = 0.0016), FOXP3+ (p = 0.00075), and CD163+ (p = 0.0011) immune cells within their microenvironments. Overall survival was significantly decreased in the cohort of patients with PM co-expressing CD70 and PD-L1 (p < 0.0001). In vitro experiments revealed that PD-L1 and CD70 additively enhanced the motility and invasiveness of PM cells. In contrast, PM cell proliferation was suppressed by PD-L1. PD-L1 enhanced mesenchymal phenotypes such as N-cadherin up-regulation. Collectively, these findings suggest that CD70 and PD-L1 both enhance the malignant phenotypes of PM and diminish anti-tumour immune responses. Based on our observations, combination therapy targeting these signalling pathways might be useful in patients with PM.

Keywords: CD70; PD-L1 (CD274); cellular proliferation; immune evasion; immunohistochemistry; invasion; migration; pleural mesothelioma.

MeSH terms

  • B7-H1 Antigen / genetics
  • CD27 Ligand / genetics
  • Forkhead Transcription Factors
  • Humans
  • Lung Neoplasms* / pathology
  • Mesothelioma* / drug therapy
  • Mesothelioma* / pathology
  • Mesothelioma, Malignant*
  • Pleural Neoplasms*
  • Programmed Cell Death 1 Receptor
  • Tumor Microenvironment


  • Programmed Cell Death 1 Receptor
  • B7-H1 Antigen
  • Forkhead Transcription Factors
  • CD274 protein, human
  • CD70 protein, human
  • CD27 Ligand