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Updated: Nov 26, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Comprehensive genomic and immunophenotypic analysis of CD4 T cell infiltrating human triple-negative breast cancer
He Zhang1, Guohui Qin2, Hui Yu3
1Key Laboratory of Tumor Immunity, Center of Infection and Immunization, Department of Immunology, School of Basic Medical Sciences, Cancer Hospital Affiliated To Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.
Abstract:
The aim of this study is to investigate the gene expression module of tumor-infiltrating CD4+T cells and its potential roles in modulating immune cell functions in triple-negative breast cancer. Differentially expressed genes were identified by comparison of the expression profile in CD4+T cells isolated from tumor tissues and peripheral blood of TNBC patients respectively. The differential expression analysis was conducted using R, and then the functional and pathway enrichment of the DEGs were analyzed using GSEA, followed by integrated regulatory network construction and genetic analysis of tumor-infiltrating immune cells based on a scientific deconvolution algorithm. As a result, abundant Treg and exhausted lymphocytes were detected, accompanied by largely decreased of effector/memory and cytotoxic T cells. Immune-related gene correlation analysis showed that the extent of follicular helper T cells gene expression signatures were inversely associated with those of CD4+ naive T cells and CD4+ memory resting T cells, but positively correlated with that of CD4+ memory activated T cells. In addition, we found five core genes including IFNG, CTLA4, FAS, CXCR6, and JUN were significantly over expressed in CD4+ TILs which may contribute to exhaustion of lymphocytes and participate in biological processes associated with regulation of chemotaxis. Study provides a comprehensive understanding of the roles of DEGs associated with the chemotactic and exhausted immunophenotypes of CD4+ TILs that are a valuable resource from which future investigation may be carried out to better understand the mechanisms that promote TNBC progression.
Insights
This study reveals key gene expression changes in CD4+ T cells within triple-negative breast cancer tumors, highlighting immune cell exhaustion and altered functions. These findings offer insights into tumor progression and potential therapeutic targets.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted therapies.
- Tumor-infiltrating lymphocytes (TILs), particularly CD4+ T cells, play a complex role in cancer immunity.
- Understanding the gene expression profiles of CD4+ TILs is crucial for deciphering their functional impact on TNBC.
Purpose of the Study:
- To investigate the gene expression module of tumor-infiltrating CD4+ T cells in TNBC.
- To identify differentially expressed genes (DEGs) and their functional roles in modulating immune cell functions.
- To explore the regulatory networks and genetic underpinnings of CD4+ TILs in TNBC.
Main Methods:
- Isolation and gene expression profiling of CD4+ T cells from TNBC tumor tissues and peripheral blood.
- Differential gene expression analysis using R.
- Functional and pathway enrichment analysis via Gene Set Enrichment Analysis (GSEA).
- Construction of integrated regulatory networks and genetic analysis using a deconvolution algorithm.
Main Results:
- TNBC tumors showed abundant regulatory T cells (Tregs) and exhausted lymphocytes, with decreased effector/memory and cytotoxic T cells.
- Follicular helper T cell gene expression inversely correlated with naive and resting memory CD4+ T cells, but positively with activated memory CD4+ T cells.
- Five core genes (IFNG, CTLA4, FAS, CXCR6, JUN) were overexpressed in CD4+ TILs, potentially driving lymphocyte exhaustion and chemotaxis regulation.
Conclusions:
- The study provides a comprehensive view of DEGs associated with chemotactic and exhausted CD4+ TIL immunophenotypes in TNBC.
- These findings highlight the critical roles of specific genes in immune cell dysfunction within the TNBC microenvironment.
- This research serves as a valuable resource for future investigations into TNBC progression mechanisms.
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