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Published on: February 8, 2018
A Pan-Cancer Analysis of CD161, a Potential New Immune Checkpoint
Xiaohan Zhou1, Jun Du2, Chengdong Liu3
1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Background:
CD161, encoded by killer cell lectin-like receptor B1 gene, is a newly reported candidate inhibitor of tumour-infiltrating T cells. Antibody-mediated CD161 blockade enhances T cell-mediated killing of cancer cells in vitro and in vivo in several tumour types. We evaluated the role of CD161 using The Cancer Genome Atlas (TCGA) Pan-Cancer Data.
Methods:
CD161 expression was analysed using RNAseq data from TCGA and the Genotype-Tissue Expression (GTEx) database. HPA, GeneCards, and String database were used to explore the protein information of CD161. The prognostic value of CD161 was analysed using clinical survival data from the TCGA. Enrichment analysis of CD161 was conducted using the R package "clusterProfiler". We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases and performed a correlation analysis between immune cell infiltration levels and CD161 expression. We further assessed the association between CD161 and immune checkpoints, immune activating genes, immunosuppressive genes, chemokines, and chemokine receptors.
Findings:
CD161 was differentially expressed and predicted better survival status in most tumour types in TCGA. In addition, CD161 expression was significantly associated with immunoregulatory interactions between lymphoid and non-lymphoid cells. CD161 expression was closely correlated with T cell infiltration, immune checkpoints, immune activating genes, immunosuppressive genes, chemokines, and chemokine receptors.
Interpretation:
Our results suggest that CD161 is a potential cancer biomarker. CD161 might synergize with other immune checkpoints to regulate the immune microenvironment, which could be applied in the development of new-targeted drugs for immunotherapy.
Funding:
This work was supported by the National Nature Science Foundation of China (grant numbers 81773008, 81672756, 81872399, 81972897), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015), the Natural Science Foundation of Guangdong Province (grant number 2017A030311023), the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program: 2017BT01S131 and the Guangzhou Technology Project (grant number 201804010044), National Key R&D Program of China (Grant Nos. 2020YFC2006400), Key-Area Research and Development Program of Guangdong Province (2019B020227004).
Insights
CD161, an inhibitor of tumor-infiltrating T cells, is a promising cancer biomarker. Its blockade enhances anti-tumor immunity, suggesting potential for novel cancer immunotherapies.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- CD161 (killer cell lectin-like receptor B1) inhibits tumor-infiltrating T cells.
- Blocking CD161 enhances cancer cell killing in vitro and in vivo.
Purpose of the Study:
- Evaluate the role of CD161 in cancer using The Cancer Genome Atlas (TCGA) Pan-Cancer Data.
- Investigate CD161's prognostic value and association with immune cell infiltration and regulatory networks.
Main Methods:
- Analyzed CD161 expression using TCGA and GTEx RNAseq data.
- Explored CD161 protein information via HPA, GeneCards, and String databases.
- Assessed prognostic value, immune cell infiltration, and associations with immune checkpoints and related genes.
Main Results:
- CD161 was differentially expressed and predicted better survival in most TCGA tumor types.
- CD161 expression correlated with T cell infiltration and immunoregulatory interactions.
- Significant associations found between CD161 and immune checkpoints, activating/suppressive genes, chemokines, and receptors.
Conclusions:
- CD161 is a potential cancer biomarker.
- CD161 may synergize with immune checkpoints to modulate the tumor immune microenvironment.
- CD161 represents a potential target for developing novel cancer immunotherapies.
