PD-L2 overexpression on tumor-associated macrophages is one of the predictors for better prognosis in lung adenocarcinoma.
Eri MatsubaraYusuke ShinchiYoshihiro KomoharaHiromu YanoCheng PanYukio FujiwaraKoei IkedaMakoto SuzukiPublished in: Medical molecular morphology (2023)
Immunotherapies that target programmed cell death protein 1 (PD-1) signals are standard therapies for advanced-stage lung cancer, and the expression of programmed death-ligand 1 (PD-L1) in cancer tissue predicts immunotherapy efficacy. Although programmed death-ligand 2 (PD-L2) is expressed in cancer cells and macrophages, similar to PD-L1, its significance in lung cancer is unclear. Double immunohistochemistry analyses using anti-PD-L2 and anti-PU.1 antibodies were carried out on tissue array sections from 231 cases of lung adenocarcinoma, and PD-L2 expression in macrophages was evaluated. High PD-L2 expression in macrophages was associated with longer progression-free survival (PFS) and cancer-specific survival (CSS) and observed more often in females, non-heavy smokers, and patients with epidermal growth factor receptor (EGFR) mutations and those at a lower disease stage. Significant correlations were found more frequently in patients with EGFR mutations. Cell culture studies revealed that cancer cell-derived soluble factors induced PD-L2 overexpression in macrophages, suggesting the involvement of the JAK-STAT signaling pathway. The present findings suggest that PD-L2 expression in macrophages predicts PFS and CSS in lung adenocarcinoma without immunotherapy.
Keyphrases
- epidermal growth factor receptor
- papillary thyroid
- free survival
- tyrosine kinase
- small cell lung cancer
- signaling pathway
- squamous cell
- advanced non small cell lung cancer
- lymph node metastasis
- transcription factor
- poor prognosis
- squamous cell carcinoma
- high resolution
- epithelial mesenchymal transition
- young adults
- long non coding rna
- endothelial cells