Evaluation of multiple immune cells and patient outcomes in esophageal squamous cell carcinoma

Hui Wang; Chanjuan Su; Ziteng Li; Changchun Ma; Liangli Hong; Zhe Li; Xiaonan Ma; Yien Xu; Xiaolong Wei; Yiqun Geng; Weifeng Zhang; Penghao Li; Jiang Gu

doi:10.3389/fimmu.2023.1091098

Evaluation of multiple immune cells and patient outcomes in esophageal squamous cell carcinoma

Front Immunol. 2023 Feb 20:14:1091098. doi: 10.3389/fimmu.2023.1091098. eCollection 2023.

Authors

Hui Wang¹, Chanjuan Su¹, Ziteng Li¹, Changchun Ma², Liangli Hong¹, Zhe Li¹, Xiaonan Ma¹, Yien Xu², Xiaolong Wei³, Yiqun Geng¹, Weifeng Zhang¹, Penghao Li^{1

4}, Jiang Gu^{1

4}

Affiliations

¹ Provincial Key Laboratory of Molecular Pathology and Personalized Medicine, Center of Collaborative and Creative Center, Department of Pathology and Pathophysiology, Shantou University Medical College, Shantou, Guangdong, China.
² Department of Radiation Oncology, Affiliated Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, China.
³ Department of Pathology, Affiliated Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, China.
⁴ Jinxin Research Institute for Reproductive Medicine and Genetics, Xinan Hospital for Maternal and Child Health Care, Chengdu, China.

Abstract

Recent reports indicate that immune cells in solid cancers have significant predictive and therapeutic value. IgG4 is a subclass of IgG and we recently found that it exerted an inhibitory effect in tumor immunity. We aimed to assess the significance of IgG4 and T cell subtypes in tumor prognosis. We investigated the density, distribution and relationship of five immune markers CD4, CD8, Foxp3, IL-10 and IgG4 with multiple immunostaining method in 118 esophageal squamous cell carcinoma (ESCC) together with clinical data. The relationship among different immune cell types and with clinical data were analyzed with Kaplan-Meier survival analysis and Cox proportional hazards model to identify independent risk factors among immune and clinicopathological parameters. Five-year survival rate of these patients treated with surgery reached 61%. Higher number of CD4⁺ plus CD8⁺ T cells predicted better prognosis (p=0.01) in tertiary lymphoid structure (TLS) and could add to the value of TNM staging. Density of the newly identified immune inhibitor IgG4⁺ B lymphocytes was found positively correlated to that of CD4⁺ cells (p=0.02) and IL-10⁺ cells (p=0.0005), but number of infiltrating IgG4⁺ cells by itself was not an independent factor for prognosis. However, increased serum concentration of IgG4 indicated a poor prognosis of ESCC (p=0.03). 5-year survival rate of esophageal cancer after surgery has been significantly improved. Increased T cells in TLS predicted better survival, suggesting that T cells in TLS may actively participate in anti-tumor immunity. Serum IgG4 could be a useful predictor of prognosis.

Keywords: CD4+ T lymphocyte; CD4+Foxp3+ regulatory T lymphocyte; CD8+ T lymphocyte; esophageal squamous cell carcinoma; immunoglobulin G4; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Carcinoma, Squamous Cell* / pathology
Esophageal Neoplasms* / pathology
Esophageal Squamous Cell Carcinoma*
Humans
Interleukin-10

Substances

Interleukin-10

Grants and funding

This work was supported by the National Natural Science Foundation of China (No.81872334) to Professor JG, the Li Kashing Foundation Cross-Disciplinary Research Program (No. 2020LKSFG12B) to LH, and Postdoctoral Research Start-up Foundation of Shantou University Medical College (N0. 510859029) to HW.