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Updated: Jul 9, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Correlation between IL3 signaling pathway-related genes and immune checkpoint inhibitor efficacy in patients with
Background:
There is a lack of effective biomarkers that predict immunotherapy efficacy in clear cell renal cell carcinoma(KIRC).
Objective:
We aimed to identify biomarkers that would predict the efficacy of KIRC treatment with immune checkpoint inhibitors (ICIs).
Methods:
Cohort data of KIRC patients with somatic mutations, mRNA expression and survival data from The Cancer Genome Atlas (TCGA) database and immunotherapy cohort and Genomics of Drug Sensitivity in Cancer (GDSC) database were analyzed and divided into interleukin 3 (IL3) pathway-related genes high expression (IL3-High) and IL3 pathway-related genes low expression (IL3-Low) groups according to pathway expression status to assess the relationship between the IL3 pathway-related genes activation status and the prognosis of KIRC patients treated with ICIs. The data were validated by immunohistochemistry experiments, and possible mechanisms of action were explored at the level of gene mutation landscape, immune microenvironment characteristics, transcriptome and copy number variation(CNV) characteristicsRESULTS: The IL3 pathway-related genes was an independent predictor of the efficacy of ICIs in KIRC patients, and the IL3-High group had a longer overall survival (OS); KIRC patients in the IL3-High group had increased levels of chemokines, cytolysis, immune checkpoint gene expression and abundant immunity. The IL3-Low group had poor immune cell infiltration and significant downregulation of complement activation, cytophagy, B-cell activation, and humoral immune response pathways. The high group was more sensitive to targeted drugs of some signaling pathways, and its efficacy in combining these drugs with immunity has been predicted in the published literature.
Conclusion:
The IL3 pathway-related genes can be used as a predictor of the efficacy of ICIs in KIRC. The IL3 pathway-related genes may affect the therapeutic efficacy of ICIs by affecting the expression of immune-related molecules, immune cell infiltration, and the level of immune response pathways.
Insights
Interleukin 3 (IL3) pathway-related genes predict immunotherapy effectiveness in clear cell renal cell carcinoma (KIRC). High IL3 pathway gene expression is linked to better outcomes and stronger immune responses in KIRC patients treated with immune checkpoint inhibitors (ICIs).
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Effective biomarkers for predicting immunotherapy response in clear cell renal cell carcinoma (KIRC) are currently lacking.
- Identifying such biomarkers is crucial for optimizing treatment strategies for KIRC patients.
Purpose of the Study:
- To identify biomarkers that can predict the efficacy of immune checkpoint inhibitor (ICI) treatment in KIRC.
- To investigate the role of Interleukin 3 (IL3) pathway-related genes in predicting ICI efficacy and patient prognosis in KIRC.
Main Methods:
- Analysis of KIRC patient data from The Cancer Genome Atlas (TCGA) and immunotherapy cohorts (GDSC) including somatic mutations, mRNA expression, and survival data.
- Patients were stratified into high (IL3-High) and low (IL3-Low) expression groups based on IL3 pathway-related genes.
- Validation through immunohistochemistry and exploration of mechanisms via gene mutation landscape, immune microenvironment, transcriptome, and copy number variation (CNV).
Main Results:
- IL3 pathway-related genes emerged as an independent predictor of ICI efficacy in KIRC.
- The IL3-High group demonstrated significantly longer overall survival (OS), increased chemokine levels, enhanced cytolysis, higher immune checkpoint gene expression, and a more robust immune infiltrate.
- Conversely, the IL3-Low group exhibited poor immune cell infiltration and downregulation of key immune response pathways, including complement activation and B-cell activation.
Conclusions:
- IL3 pathway-related genes serve as a valuable predictor for ICI treatment efficacy in KIRC.
- Activation of the IL3 pathway influences therapeutic outcomes by modulating immune-related molecules, immune cell infiltration, and immune response pathways in KIRC.
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