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Research Paper|Volume 15, Issue 21|pp 12369—12387

CCL19: a novel prognostic chemokine modulates the tumor immune microenvironment and outcomes of cancers

Qiang Gu1, Shifang Zhou2, Cong Chen3, Zhi Wang4, Wenhao Xu5, Jiarong Zhang2, Shiyin Wei6, Jianfeng Yang7, Hongjing Chen1
  • 1Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong 226000, China
  • 2Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
  • 3Department of Nursing, Fudan University Shanghai Cancer Center, Shanghai 201321, China
  • 4Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China
  • 5Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • 6Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
  • 7Department of Surgery, Shangnan Branch of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200126, China
* Equal contribution
Received: June 19, 2023Accepted: October 6, 2023Published: November 8, 2023
https://doi.org/10.18632/aging.205184

Copyright: © 2023 Gu 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.

Abstract

Background: CCL19 is a chemokine involved in cancer research due to its important role in the tumor microenvironment (TME) and clinical relevance in cancers. This study aimed to analyze transcription expression, genomic alteration, association with tumor immune microenvironment of CCL19 expression and its prediction value for prognosis and responses to immunotherapy for patients with cancers.

Methods: RNA sequencing data and corresponding clinicopathological information of a total of large-scale cancer patients were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. Multiplex immunofluorescence (mIF) was implemented to identify differential infiltration of Treg, CD8+ T cells, and tumor-associated macrophages, while CCL19 immunohistochemistry was conducted on 182 breast cancer samples from a real-world cohort.

Results: Based on large-scale multi-center survival analysis of cancer patients, we found the prognosis of patients with high CCL19 expression was prominently better than those with low CCL19 expression. For patients from multiple independent cohorts, suppressed CCL19 expression exerts significant progressive phenotype and apoptosis activity of cancers, especially in breast and ovarian cancer. Interestingly, anti-tumor immune cells, specifically the CD8+ T cells and macrophages, were clustered from TME by elevated CCL19 expression. Additionally, higher CCL19 levels reflected heightened immune activity and substantial heterogeneity.

Conclusions: In conclusion, our findings support the notion that elevated CCL19 expression is linked to favorable outcomes and enhanced anti-tumor immunity, characterized by increased CD8+ T cells within the TME. This suggests the potential of CCL19 as a prognostic marker, predictive biomarker for immunotherapy, therapeutic target of cancers.