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Journal of Cancer Research and Clinical Oncology

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Open Access 01-03-2024 | Gastric Cancer | Research

Analyzing the associations between tertiary lymphoid structures and postoperative prognosis, along with immunotherapy response in gastric cancer: findings from pooled cohort studies

Authors: Haoxin Peng, Xiangrong Wu, Cheng Zhang, Yueting Liang, Siyuan Cheng, Honglang Zhang, Lin Shen, Yang Chen

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2024

Abstract

Background

The clinical significance of tertiary lymphoid structure (TLS) in gastric cancer (GC) was uncertain.

Methods

A systematic search was performed in public databases for eligible studies as of April 2, 2023. Meta-analyses were performed to interrogate the associations between TLS levels and prognosis and immunotherapy response of GC. Bioinformatic analyses based on the nine-gene signature of TLS were further conducted to capture the biological underpinnings.

Results

Eleven studies containing 4224 GC cases were enrolled in the meta-analysis. TLS levels positively correlated with smaller tumor size, earlier T stage and N stage. Moreover, higher TLS levels were detected in diffuse and mix subtypes of GC (P < 0.001). Higher TLS levels strongly predicted favorable postoperative overall survival of GC, with HR of 0.36 (95%CI 0.26–0.50, P < 0.001) and 0.55 (95%CI 0.45–0.68, P < 0.001) of univariate and multivariate Cox analysis, respectively. Higher TLS levels were also in favor of the treatment response of anti-PD-1 inhibitors as later-line therapy of GC. TLS levels positively correlated with immune effector cells infiltration, diversity and richness of T cell receptor and B cell receptor repertoire, immune checkpoint genes expression, and immune-related genes mutation of GC in the TCGA-STAD cohort, representing higher immunogenicity and immunoactivity. Moreover, moderate accuracy of TLS levels in predicting benefit from anti-PD-1 inhibitors in the PRJEB25780 cohort was also validated (AUC 0.758, 95%CI 0.583–0.933), higher than the microsatellite instability-score and Epstein-Barr virus status.

Conclusions

TLS levels demonstrated potential in predicting the postoperative prognosis and immunotherapy response of GC.

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Title: Analyzing the associations between tertiary lymphoid structures and postoperative prognosis, along with immunotherapy response in gastric cancer: findings from pooled cohort studies
Authors: Haoxin Peng
Xiangrong Wu
Cheng Zhang
Yueting Liang
Siyuan Cheng
Honglang Zhang
Lin Shen
Yang Chen
Publication date: 01-03-2024
Publisher: Springer Berlin Heidelberg
Keywords: Gastric Cancer
Gastric Cancer
Checkpoint Inhibitors
Published in: Journal of Cancer Research and Clinical Oncology / Issue 3/2024
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-024-05672-y

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