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Updated: Aug 11, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Identification of IRF-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological
Can Chen1,2, Lin-Yuan Chen1,2, Rui-Xia Yang1,2
1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Background:
Recently studies have identified a critical role for interferon regulatory factor (IRF) in modulating tumour immune microenvironment (TME) infiltration and tumorigenesis.
Methods:
Based on IRF1-9 expression profiles, we classified all ccRCC samples into three molecular subtypes (clusters A-C) and characterized the prognosis and immune infiltration of these clusters. IRFscore constructed by principal component analysis was performed to quantify IRF-related subtypes in individual patients.
Results:
We proved that IRFscore predicted multiple patient characteristics, with high IRFscore group having poorer prognosis, suppressed TME, increased T-cell exhaustion, increased TMB and greater sensitivity to anti- PD-1/CTLA-4 therapies. Furthermore, analysis of metastatic ccRCC (mccRCC) molecular subtypes and drug sensitivity proved that low IRFscore was more sensitive to targeted therapies. Moreover, IRFscore grouping can be well matched to the immunological and molecular typing of ccRCC. qRT-PCR showed differential expression of IRFs in different cell lines.
Conclusions:
Evaluating IRF-related molecular subtypes in individual ccRCC patients not only facilitates our understanding of tumour immune infiltration, but also provides more effective clinical ideas for personalised treatment.
Insights
Interferon regulatory factor (IRF) subtypes in kidney cancer (ccRCC) impact prognosis and immune microenvironment. IRFscore predicts patient characteristics and guides personalized therapies, including immunotherapy and targeted treatments.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Interferon regulatory factors (IRFs) play a crucial role in regulating the tumor immune microenvironment (TME) and tumorigenesis.
- Understanding IRF expression is vital for dissecting tumor behavior and immune interactions.
Purpose of the Study:
- To classify ccRCC samples into molecular subtypes based on IRF expression.
- To develop a quantitative measure (IRFscore) for assessing IRF-related subtypes in individual patients.
- To correlate IRF subtypes with prognosis, immune infiltration, and therapeutic sensitivity.
Main Methods:
- Classification of ccRCC samples into three molecular subtypes (A-C) using IRF1-9 expression profiles.
- Development of an IRFscore using principal component analysis to quantify IRF-related subtypes.
- Analysis of patient characteristics, TME, T-cell exhaustion, TMB, and drug sensitivity across IRFscore groups.
Main Results:
- High IRFscore was associated with poorer prognosis, suppressed TME, increased T-cell exhaustion, higher TMB, and better response to anti-PD-1/CTLA-4 therapies.
- Low IRFscore in metastatic ccRCC (mccRCC) indicated greater sensitivity to targeted therapies.
- IRFscore grouping aligned well with existing ccRCC immunological and molecular classifications.
- Differential IRF expression was observed in various ccRCC cell lines via qRT-PCR.
Conclusions:
- IRF-related molecular subtypes provide valuable insights into ccRCC immune infiltration.
- IRFscore facilitates a deeper understanding of ccRCC heterogeneity.
- This approach offers potential for more effective personalized treatment strategies in ccRCC.
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