Research Paper Volume 16, Issue 13 pp 11027—11061

Characteristics of auto-quantified tumor-infiltrating lymphocytes and the prognostic value in adenocarcinoma of the esophagogastric junction, gastric adenocarcinoma, and esophageal squamous cell carcinoma

Hao Dong1, *, , Longqing Yao2, *, , Jiahui Fan3, , Peipei Gao2,4, , Xiaorong Yang4,5, , Ziyu Yuan4, , Tiejun Zhang1,4, , Ming Lu4,5, , Xingdong Chen2,4,6, , Chen Suo1,4,7, ,

  • 1 Department of Epidemiology and Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China
  • 2 State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China
  • 3 Department of Clinical Laboratory, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
  • 4 Fudan University Taizhou Institute of Health Sciences, Taizhou, China
  • 5 Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China
  • 6 Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, China
  • 7 Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
* Co-first authors

Received: October 4, 2023       Accepted: June 10, 2024       Published: July 5, 2024
How to Cite

Copyright: © 2024 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Adenocarcinoma of the esophagogastric junction (AEGJ) with a specific pathological profile and poor prognosis has limited therapeutic options. Previous studies have found that TILs exhibit distinct characteristics in different tumors and are correlated with tumor prognosis. We established cellular training sets to obtain auto-quantified TILs in pathological images. And we compared the characteristics of TILs in AEGJ with those in esophageal squamous cell carcinoma (ESCC) and gastric adenocarcinoma (GAC) to gain insight into the unique immune environments of these three tumors and investigate the prognostic value of TILs in these three tumors.

Methods: Utilizing a case-control study design, we analyzed 214 AEGJ, 256 GAC, and 752 ESCC cases. The TCGA dataset was used to validate prognostic value of auto-quantified TILs. The specific cellular training sets were established by experienced pathologists to determine TILs counts. Kruskal-Wallis test and multi-variable linear regression were conducted to explore TILs characteristics. Survival analyses were performed with Kaplan-Meier method and Cox proportional hazards model.

Results: The three cellular training sets of these cancers achieved a classification accuracy of 87.55 at least. The median auto-quantified TILs of AEGJ, GAC, and ESCC cases were 4.82%, 1.92%, and 0.12%, respectively. The TILs demonstrated varied characteristics under distinctive clinicopathological traits. The higher TILs proportion was associated with better prognosis in esophagogastric cancers (all P < 0.05) and was an independent prognostic biomarker on AEGJ in both datasets (Taixing: HR = 0.965, 95% CI = 0.938–0.994; TCGA: HR = 0.811, 95% CI = 0.712–0.925).

Conclusions: We found variations in TILs across ESCC, GAC, and AEGJ, as assessed by image processing algorithms. Additionally, TILs in these three cancers are an independent prognostic factor. This enhances our understanding of the unique immune characteristics of the three tumors, improving patient outcomes.


AEGJ: Adenocarcinoma of the Esophagogastric Junction; aHR: adjusted HR; ESCC: Esophageal Squamous Cell Carcinoma; GAC: Gastric Adenocarcinoma; OS: Overall Survival; SVM: Support Vector Machine; TILs: Tumor-Infiltrating Lymphocytes.