Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological type of esophageal cancer, predominantly constituting 90% of cases worldwide. Despite the development of multidisciplinary therapeutic approaches, its prognosis remains unfavorable. Recently, the development of monoclonal antibodies inhibiting programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) has led to marked therapeutic responses among multiple malignancies including ESCC. However, only a few patients achieved clinical benefits due to resistance. Therefore, precise and accurate predictive biomarkers should be identified for personalized immunotherapy in clinical settings. Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD-L1 expression on tumors, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.

Keywords: esophageal cancer; immune checkpoint inhibitors; immune microenvironment; squamous cell carcinoma; tumor immunity.

Figure 1

Cancer resistance to immune checkpoint inhibitors can be driven both by tumor cell‐intrinsic and tumor cell‐extrinsic factors

Figure 2

Schematic view of the tumor immune microenvironment. MDSC, myeloid‐derived suppressor cell; TAM, tumor‐associated macrophages

Figure 3

A, Multiplex immunofluorescence for PD‐1 and PD‐L2 expression on tumor cells B, Four subtypes of tumor immune microenvironments based on the presence or absence of tumor‐infiltrating lymphocytes (TILs) and PD‐L1 expression. C, Multiplex immunofluorescence for PD‐1 expression on TILs and PD‐L1 status on tumor cells