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Oncogene and cytokine expression of human colorectal tumors responding to immunotherapy
T Doran1, H Stuhlmiller, J A Kim
1Ohio State University Arthur G. James Cancer Hospital and Research Institute, Columbus, USA.
Abstract:
Tumor samples from five patients with metastatic colorectal cancer who demonstrated tumor regressions in clinical trials of interleukin (IL)-1 beta, IL-2, and adoptive cellular therapy were analyzed for oncogene and cytokine mRNA expression. Tumors from eight nonresponding patients were also studied. Mutations of the ras protooncogene and overexpression of c-myc protooncogene were observed in both responding and nonresponding tumors. In contrast, none of the responding tumors expressed transforming growth factor (TGF)-beta 1 mRNA, whereas nonresponding tumors did. The expression of IL-1, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, granulocyte macrophage-colony-stimulating factor, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, macrophage chemotactic protein, and RANTES was variable between responding and nonresponding patients. Although we cannot conclude that a pattern of oncogene and/or cytokine mRNA expression specifically characterizes sensitive colorectal cancers, these analyses-the assessment of TGF-beta 1 mRNA in particular-merit further evaluation as biomarkers prognostic of immunotherapy response.
Insights
Transforming growth factor-beta 1 (TGF-beta 1) mRNA absence may predict immunotherapy response in metastatic colorectal cancer. This finding, alongside other cytokine and oncogene expressions, warrants further investigation as a potential biomarker.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Metastatic colorectal cancer (mCRC) remains a significant health challenge.
- Interleukin (IL)-based immunotherapy and adoptive cellular therapy show promise but require predictive biomarkers.
- Understanding oncogene and cytokine expression in tumors can guide treatment strategies.
Purpose of the Study:
- To analyze oncogene and cytokine mRNA expression in tumors from patients with metastatic colorectal cancer.
- To identify potential molecular markers that predict response to immunotherapy.
- To investigate the role of transforming growth factor-beta 1 (TGF-beta 1) in immunotherapy outcomes.
Main Methods:
- Analysis of tumor samples from mCRC patients who responded or did not respond to IL-1 beta, IL-2, and adoptive cellular therapy.
- Quantitative assessment of mRNA expression for specific oncogenes (ras, c-myc) and various cytokines (IL-1, IL-6, IL-8, IL-10, TNF-alpha, GM-CSF, MIP-1 alpha, MIP-1 beta, MCP, RANTES, TGF-beta 1).
Main Results:
- Ras protooncogene mutations and c-myc protooncogene overexpression were present in both responding and nonresponding tumors.
- None of the responding tumors expressed TGF-beta 1 mRNA, while it was detected in nonresponding tumors.
- Expression of other cytokines (IL-1, IL-6, IL-8, IL-10, TNF-alpha, GM-CSF, MIP-1 alpha, MIP-1 beta, MCP, RANTES) varied between groups.
Conclusions:
- TGF-beta 1 mRNA expression may serve as a potential biomarker for predicting immunotherapy response in colorectal cancer.
- While oncogene mutations and overexpression were common, TGF-beta 1 absence appears more specifically linked to treatment sensitivity.
- Further research is needed to validate TGF-beta 1 as a prognostic biomarker for immunotherapy in mCRC.