Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1)

Abstract

Programmed death-1 (PD-1) is a coinhibitory inducible receptor present on T-cells and macrophages. Tumor cells with increased programmed death ligand-1 (PD-L1) are believed to escape immunity through activation of PD-1/PD-L1 pathway and suppression of effector-immune responses. Recent strategies targeting the PD-1/PD-L1 axis have shown promising results in patients with several tumors types, including lung carcinomas. Preliminary data suggest that PD-L1 protein expression might have predictive response to such therapies. Sarcomatoid carcinomas (SCs) of the lung include rare subtypes of poorly differentiated non-small-cell lung carcinomas of high grade and aggressive behavior. The biology of these neoplasms is poorly understood and they frequently show increased local inflammatory and lymphocytic infiltration. Here, we report the expression of PD-L1 in 13 SCs from two large retrospective lung cancer cohorts. Using automated quantitative immunofluoresence and a mouse monoclonal antibody directed against the extracellular domain of PD-L1, we show that 9 of 13 patients (69.2%) with SCs are positive for PD-L1 and their levels are higher than in conventional non-small-cell lung carcinoma. These results provide rationale for the potential use of targeted immunotherapy in lung SCs.

Figure 1. Sarcomatoid lung carcinomas show increased PD-L1 protein levels

A) Representative microphotographs showing PD-L1 and cytokeratin positivity in Giant Cell lung carcinoma. Left panels include Hematoxilin & Eosin stained preparations at 200x (upper) and 400x magnification (lower panel). Giant cell carcinomas show characteristic lack of typical epithelial cohesiveness, a prominent mixed inflammatory infiltrate and bizarre giant tumor cells with single/multiple nuclei and focal leukocyte engulfment (emperipolesis, arrows). The right panels show fluorescence captions of PD-L1 (upper, red channel) and cytokeratin (lower, green channel) positivity of the same sample. Nuclei were stained with DAPI (blue channel). B) Representative fluorescence microphotographs showing PD-L1 staining in FFPE term human placenta (upper panels) and Mel624 transfectants (lower panels). PD-L1 positivity in placental samples was restricted to the trophoblastic cells (cytokeratin positive compartment, CK, right panel) and absent in the stromal areas (vimentin positive compartment, Vim, left panel). Bar=100 μm. In the cell lines, PD-L1 signal was evident with a perinuclear/membranous pattern only in PD-L1 transfected Mel624 cells (bottom right panel) but not in parental cells (bottom left panel). Bar=50 μm. C) Graph showing mean ± SEM PD-L1 AQUA scores in conventional NSCLC (left bar) and in Sarcomatous carcinomas (right bar). AQUA scores are expressed as arbitrary units (AU). Cases were measured in the same preparations. The number of cases in each group is indicated within each bar. **=p<0.01