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Updated: Jun 17, 2026
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Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Transcriptomic profiling identifies immunotherapy-responsive phenotypes in microsatellite-stable metastatic
Tomas Konecny1,2, Nate Zadirako1,3, Arpine Grigoryan1
1Armenian Bioinformatics Institute (ABI), Yerevan, Armenia.
Oncogene
|June 15, 2026
Summary
This study reveals four molecular subtypes in microsatellite-stable metastatic colorectal cancer (MSS mCRC), identifying specific tumor microenvironments that predict response to novel immunotherapy. These findings may help expand treatment efficacy for patients with MSS mCRC.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Microsatellite-stable metastatic colorectal cancer (MSS mCRC) shows resistance to conventional immune checkpoint inhibitors (ICIs).
- Tumor immunogenicity and heterogeneity contribute to therapeutic resistance in MSS mCRC.
- Botensilimab (Fc-enhanced anti-CTLA-4) and balstilimab (anti-PD-1) are novel immunotherapies being investigated.
Purpose of the Study:
- To analyze transcriptomic profiles of MSS mCRC tumors treated with botensilimab ± balstilimab.
- To identify molecular subtypes and their correlation with immunotherapy response.
- To understand the tumor microenvironment's role in treatment resistance and efficacy.
Main Methods:
- Comprehensive transcriptomics analysis of primary and metastatic MSS mCRC tumor biopsies.
- Application of Self-Organizing Map (SOM) machine learning for tumor stratification.
- Correlation of molecular subtypes with clinical response and survival data.
Main Results:
- Four molecular tumor types (liver-like, proliferative, inflammatory, mesenchymal) were identified.
- Tumor types showed distinct cellular compositions and microenvironment states.
- Inflammatory and mesenchymal types demonstrated improved clinical responses and survival compared to liver-like and proliferative types.
- Treatment induced transcriptomic shifts towards immune-enriched states.
Conclusions:
- Distinct tumor microenvironment states in MSS mCRC are associated with immunotherapy response.
- Molecular subtypes identified can inform patient stratification for novel immunotherapies.
- Findings provide insights into expanding ICI efficacy in previously unresponsive MSS mCRC tumors.
