Expression and potential role of CCL4 in CD8+T cells in NSCLC
Ran Chen1, Li Ma1, Chang Jiang1
1Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Purpose:
Under the continuous stimulation of tumor antigen in the tumor microenvironment, CD8+T cells will enter a state of functional defect or failure, which cannot effectively prevent the progression of lung cancer. Therefore, finding potential targets for immunotherapy in lung cancer has broad prospects.
Methods:
In the early stage of this study, the genes related to immune infiltration in lung cancer were found through the analysis on multiple datasets (GSE116959, GSE139032 and GSE111894). Characteristics of candidate genes were identified from transcriptome, methylation, single cell sequencing and other dimensions, respectively. Moreover, the correlation between candidate genes and immunotherapy-related genes and mutated genes of lung cancer was further identified. Finally, the expression of the candidate genes was detected with an online immunohistochemistry database.
Results:
According to the above research, it was found that CCL4 (chemokine (C-C motif) ligand 4) was abnormally highly expressed in samples from patients with NSCLC and had certain methylation characteristics. In addition, CCL4 was also closely associated with infiltration of immune cells, such as B cells and CD8+T cells. Interestingly, the aberrant expression of CCL4 affected the survival of CD8+T cells. Single cell sequencing results also showed that CCL4 was highly expressed in CD8+T cells and was involved in biological functions such as generation cycle. Finally, CCL4 expression was positively associated with PD-1 and PD-L1, and also with mutant genes, such as EGFR, ALK and ROS1, associated with the treatment for lung cancer.
Conclusion:
CCL4 may be a potential target for immunotherapy in patients with NSCLC.
Insights
Chemokine ligand 4 (CCL4) is highly expressed in non-small cell lung cancer (NSCLC) and impacts CD8+T cell survival, suggesting CCL4 as a potential immunotherapy target for lung cancer.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Tumor microenvironment challenges CD8+T cell function in lung cancer.
- Identifying novel immunotherapy targets is crucial for effective lung cancer treatment.
Purpose of the Study:
- To identify potential therapeutic targets for lung cancer immunotherapy.
- To investigate the role of immune infiltration-related genes in non-small cell lung cancer (NSCLC).
Main Methods:
- Analyzed multiple lung cancer datasets (GSE116959, GSE139032, GSE111894) to identify immune infiltration genes.
- Evaluated candidate genes using transcriptome, methylation, and single-cell sequencing data.
- Correlated candidate genes with immunotherapy markers and lung cancer mutations, validating expression via an immunohistochemistry database.
Main Results:
- Chemokine (C-C motif) ligand 4 (CCL4) showed abnormal overexpression and specific methylation patterns in NSCLC samples.
- CCL4 expression correlated with immune cell infiltration (B cells, CD8+T cells) and affected CD8+T cell survival.
- CCL4 was highly expressed in CD8+T cells, linked to cell cycle functions, and positively associated with PD-1, PD-L1, and driver mutations (EGFR, ALK, ROS1).
Conclusions:
- CCL4 represents a potential therapeutic target for enhancing immunotherapy in NSCLC patients.
- Targeting CCL4 may restore CD8+T cell function in the lung cancer tumor microenvironment.
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