Positive Programmed Cell Death-Ligand 1 Expression Predicts Poor Treatment Outcomes in Esophageal Squamous Cell Carcinoma Patients Receiving Neoadjuvant Chemoradiotherapy

Abstract

Background: Programmed cell death-ligand 1 (PD-L1) is present in a subgroup of cancer patients who may be favorable targets for immune checkpoint inhibitor therapies. However, the significance of the PD-L1 expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy remains unclear. Methods: By means of PD-L1 immunohistochemistry 22C3 pharmDx assay, we evaluate the PD-L1 expression and its association with clinical outcome in 107 ESCC patients receiving neoadjuvant chemoradiotherapy. Results: Patients with positive PD-L1 expression have significantly lower pathological complete response rates (13% versus 32%; p = 0.036) than those with negative PD-L1 expression. Univariate survival analysis found that positive PD-L1 expression were correlated with poor overall survival (p = 0.004) and inferior disease-free survival (p < 0.001). In a multivariate analysis, positive PD-L1 expression was independently associated with the absence of a pathologically complete response (p = 0.044, hazard ratio: 3.542), worse overall survival (p = 0.006, hazard ratio: 2.017), and inferior disease-free survival (p < 0.001, hazard ratio: 2.516). Conclusions: For patients with ESCC receiving neoadjuvant chemoradiotherapy, positive PD-L1 expression independently predicts the poor chemoradiotherapy response and worse treatment outcome. Thus, our data suggests that PD-L1 may be an influential biomarker for prognostic classification and for immune checkpoint inhibitor therapies in ESCC patients receiving neoadjuvant chemoradiotherapy.

An individualized immune signature of pretreatment biopsies predicts pathological complete response to neoadjuvant chemoradiotherapy and outcomes in patients with esophageal squamous cell carcinoma

“…22 Recently, studies revealed that the expression of immune checkpoint molecules like PD-L1 and indoleamine 2,3-dioxygenase 1 from pretreatment endoscopic cancer biopsies were biomarkers that could predict pathologic response after nCRT in ESCCs. 23,24 Thus, discrepancies in immune molecular profiles, observed in different cases, may potentially comprise powerful models for nCRT prediction. However, little is known about the landscape of immune molecules in the pretreatment specimens between pCRs and <pCRs.…”

Identification of a Prognostic Immune Signature for Esophageal Squamous Cell Carcinoma to Predict Survival and Inflammatory Landscapes

“…Several recent studies have focused on immunerelated parameters to predict OS in patients with EC, including some important immune molecules and cells. The results of these studies have further indicated the significance of the immune tumor microenvironment (TME) (Huang et al, 2019;Yagi et al, 2019). Unfortunately, precision immunotherapy is hard to achieve without a comprehensive understanding of the TME immune landscape.…”

Genomic characteristics in neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma

“…A prospective study using diffusion-weighted magnetic resonance imaging showed that a higher post-nCRT apparent diffusion coefficient value could be a predictive indicator of good pathologic response to nCRT in ESCC patients (10). Another retrospective e x p l o r a t o r y s t u d y s u g g e s t e d t h a t h i g h e r P D -L 1 expression and the CD8 + and CD4+ lymphocyte ratio were more relevant to pCR in a cohort of 88 ESCC patients receiving nCRT (11), whereas another study disclosed the opposite result that positive PD-L1 expression predicted a poor nCRT response (12). Recently, we reported the results of an analysis of the NEOCRTEC5010 trial, which revealed that persistent pathologic lymph node metastasis after NCRT was significantly associated with a poor prognosis in ESCC patients (13).…”