Abstract
Data describing relationships between the tumor immune microenvironment and patient outcome are limited for esophageal squamous cell cancer (ESCC). The present study investigated the prognostic values of programmed death-ligand 1 (PD-L1) expression and CD8+ or forkhead box protein 3+ (FOXP3+) tumor-infiltrating lymphocytes (TILs) in 133 pathological T3N0M0 stage ESCC patients who underwent radical resection without neoadjuvant or adjuvant therapy. CD8+ and FOXP3+ TIL densities as well as PD-L1 levels in tumor cells and lymphocytes, were assessed through immunohistochemical staining. Patient survival was not associated with CD8+ or FOXP3+ TILs alone, but PD-L1 expression and the CD8+/FOXP3+ ratio were independent predictors of both disease-free and overall survival. PD-L1 expression correlated with age (p = 0.029), tumor length (p < 0.001), tumor differentiation status (p = 0.002) and reduced intratumoral CD8+ TIL density (p < 0.001). Our results suggest pT3N0M0 ESCC clinical outcomes correlate with CD8+ and FOXP3+ TIL densities and PD-L1 levels. Moreover, an intrinsic mechanism for induction of PD-L1 overexpression may be occurring during early tumor oncogenesis. This information may be useful for stratifying patients and guide the application of checkpoint blockade therapy in ESCC.
Highlights
Esophageal squamous cell carcinoma (ESCC) remains the predominant type of esophageal cancer (EC) in the “EC Belt”, which extends from China via central Asia to northern Iran [1]
The present study investigated the prognostic values of programmed death-ligand 1 (PD-L1) expression and CD8+ or forkhead box protein 3+ (FOXP3+) tumor-infiltrating lymphocytes (TILs) in 133 pathological T3N0M0 stage esophageal squamous cell cancer (ESCC) patients who underwent radical resection without neoadjuvant or adjuvant therapy
Our results suggest pathological T3N0M0 stage (pT3N0M0) ESCC clinical outcomes correlate with CD8+ and FOXP3+ TIL densities and PD-L1 levels
Summary
Esophageal squamous cell carcinoma (ESCC) remains the predominant type of esophageal cancer (EC) in the “EC Belt”, which extends from China via central Asia to northern Iran [1]. Patients with pathological T3N0M0 stage (pT3N0M0) disease represent a considerable fraction of middle-stage patients. They have the same TNM stage, they are divided into stages IB, IIA, and IIB based on tumor location and histologic grade in the 7th edition of the AJCC manual [4]. While one study observed improved prognosis in patients with abundant CD8+ TILs, another found no association between patient survival and CD8+ TILs in residual tumor or scar tissues [6, 7]. Multiple studies associated TILs with clinicopathological factors such as survival, response to neoadjuvant therapy and even tumor stage in www.impactjournals.com/oncotarget
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