PD-L1 expression is associated with epithelial-to-mesenchymal transition in adenocarcinoma of the lung

PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy for pulmonary adenocarcinoma (pADC). Epithelial-to-mesenchymal transition (EMT) is involved in the progression and immune evasion of cancers. Therefore, we investigated the association between PD-L1 expression and EMT phenotype in pADC. Immunohistochemistry for E-cadherin (epithelial marker), ZEB1, SNAIL, SLUG, vimentin (mesenchymal markers), PD-L1, CD8 and PD-1 was performed on 477 cases of pADC. Cases were classified into epithelial, mesenchymal, epithelial-mesenchymal, and unspecified types based on immunohistochemical results. PD-L1 expression was scored as 0 in 14.0% (n = 67), 1 in 26.4% (n = 126), 2 in 51.2% (n = 244) and 3 in 8.4% (n = 40). PD-L1 score was positively correlated with SNAIL and vimentin H-scores (P < .001, both). After dichotomizing patients into PD-L1-negative and -positive groups, PD-L1-positivity was significantly higher in patients with mesenchymal (71.2%, 84/118) and epithelial-mesenchymal (62.7%, 84/134) phenotypes compared to those with epithelial (50.6%, 44/87) and unspecified (50.0%, 35/70) phenotypes (P = .005). The significant association between PD-L1 expression and EMT phenotype was maintained in EGFR -mutated pADCs. Moreover, cases with EMT phenotype (i.e., mesenchymal and epithelial-mesenchymal) were infiltrated by higher numbers of CD8+ and PD-1+ cells than those with epithelial and unspecified phenotypes in EGFR -mutated pADCs (P = .043 for CD8+ cells and P < .001 for PD-l+ cells). Particularly, cases with EMT phenotype and PD-L1 expression showed the greatest amount of CD8+ and PD-1+ cells in EGFR -mutated cases ( P = .043 for CD8+ cells and P = .005 for PD-1+ cells). This study demonstrates that EMT phenotype is related to PD-L1 overexpression in pADC cells and patients with EMT-phenotype pADC may benefit from PD-1/PD-L1-blocking immunotherapy.