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Updated: Feb 23, 2026
Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Analysis of non-small cell lung cancer microenvironment indicates preponderance of T cell exhaustion marker
Hui Zhou1, Tingwei Liu1, Zanfeng Wang1
1Department of Respiratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China.
Abstract:
Lung cancer metastasis causes 70% of an estimated 1.4 million deaths per annum. The major shortcoming in lung cancer is the tendency to have inherent or develop acquired resistance to chemotherapy. It is now evolving that such resistance might develop due to differential contribution and interaction with tumor microenvironment, stromal cells, and the extracellular matrix. The objective of the current study was to define the lung cancer tumor microenvironment. We have identified multiple tumor-infiltrating T lymphocyte subsets in patients with lung cancer, which were independent of disease stage. Functional analysis indicated high expression of the inhibitory receptors, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activated gene 3 (LAG3) and programmed cell death protein 1 (PD-1) in both CD4 and CD8 subsets, compared to non-malignant controls. Inhibitory receptors expressed by the tumor infiltrating T cells might mediate tolerance to tumor antigens with co-expression of these receptors exacerbating lung carcinogenesis and metastatic progression.
Insights
Lung cancer
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Lung cancer metastasis is a leading cause of cancer death.
- Chemotherapy resistance is a major challenge in lung cancer treatment.
- Tumor microenvironment interactions may drive drug resistance.
Purpose of the Study:
- To define the lung cancer tumor microenvironment.
- To investigate T lymphocyte subsets in lung cancer patients.
- To analyze the expression of inhibitory receptors on tumor-infiltrating T cells.
Main Methods:
- Identification of tumor-infiltrating T lymphocyte subsets.
- Functional analysis of T cell subsets.
- Quantification of inhibitory receptor expression (CTLA4, LAG3, PD-1) on CD4+ and CD8+ T cells.
Main Results:
- Multiple tumor-infiltrating T lymphocyte subsets were identified, irrespective of disease stage.
- High expression of inhibitory receptors cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activated gene 3 (LAG3), and programmed cell death protein 1 (PD-1) was observed.
- These receptors were expressed on both CD4+ and CD8+ T cell subsets compared to controls.
Conclusions:
- Tumor-infiltrating T cells in lung cancer exhibit high expression of inhibitory receptors.
- These inhibitory receptors may contribute to immune tolerance of tumor antigens.
- Co-expression of these receptors could exacerbate lung cancer progression and metastasis.
