Abstract
Programmed death-ligand 1 (PD-L1) expression may influence the prognosis of patients with localized esophageal cancer. The current study compared the prognostic value of PD-L1 expression between tumor cells and immune cells. Archival esophageal tumor tissue samples were collected from patients who received paclitaxel and cisplatin-based neoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal squamous cell carcinoma (ESCC) in three prospective phase II trials. PD-L1 expression on tumor and immune cells was examined immunohistochemically by using the SP142 antibody and scored by two independent pathologists. The association of PD-L1 expression with patient's outcomes was analyzed using a log-rank test and Cox regression multivariate analysis. A total of 100 patients were included. PD-L1 expression on tumor cells was positive (≥ 1%, TC-positive) in 55 patients; PD-L1 expression on immune cells was high (≥ 5%, IC-high) in 30 patients. TC-positive status was associated with poor overall survival (OS) (HR: 1.63, P = 0.035), whereas IC-high status was associated with improved OS (HR: 0.44, P = 0.0024). Multivariate analysis revealed that TC-positive, IC-high, and performance status were independent prognostic factors for progression-free survival and that IC-high and performance status were independent factors for OS. Furthermore, the combination of IC-high and TC-negative status was associated with the optimal OS, whereas that of TC-positive and IC-low status was associated with the worst OS. PD-L1 expression on tumor and immune cells may have different prognostic value for patients with locally advanced ESCC receiving neoadjuvant CRT. A combination of these two indexes may further improve the prognostic prediction.
Highlights
Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant disease in East and Central Asia
TC-positive status was associated with poor overall survival (OS) (HR: 1.63, P = .035), whereas immune cells was categorized as high (IC-high) status was associated with improved OS (HR: 0.44, P = .0024)
The combination of IC-high and TC-negative status was associated with the optimal OS, whereas that of TC-positive and IC-low status was associated with the worst OS
Summary
Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant disease in East and Central Asia. At the time of diagnosis, most patients present with locally advanced disease, which can be treated with multimodal therapy with curative intent. Despite aggressive multimodal therapy, such as neoadjuvant chemoradiotherapy (CRT) plus radical esophagectomy, the long-term survival rate of patients with ESCC is only 30% to 40% (van Hagen et al 2012; Huang et al 2015). Dysregulation of PD-L1 and PD-1 signaling occurs in multiple human diseases, including cancers. Since 2014, blockade of the PD-L1/PD-1 immune checkpoint has become an important modality of cancer therapy. As of the end of 2020, multiple anti-PD-1/PD-L1 inhibitors have been approved for the treatment of more than 20 indications across cancers, including advanced ESCC (Kato et al 2019; Kojima et al 2020)
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