[Research progress on biomarkers for proficient mismatch repair/microsatellite stable colorectal cancer in the immunotherapy era]
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Updated: Jul 17, 2026
Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
M X Yan1, Y Q Wang1, L J Shen1
1Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Shanghai Key Laboratory of Radiation Oncology; Shanghai Clinical Research Center for Radiation Oncology, Shanghai 200032, China.
Abstract:
Immunotherapy based on immune checkpoint inhibitor (ICI) has shown remarkable efficacy in the treatment of microsatellite instability (MSI)-high CRC. However, the monotherapy of ICI in microsatellite stable (MSS) CRC has not been satisfactory. Some patients with MSS CRC can benefit from various combination immunotherapy regimens. Identifying appropriate biomarkers to select MSS-type CRC patients who will benefit from ICI treatment prior to therapy initiation and dynamically monitoring treatment efficacy during the therapeutic course have become crucial components of precision medicine in clinical practice. This article reviews the current research status of traditional biomarkers such as tumor mutation burden (TMB) and PD-L1 expression. It also explores the latest research progress and clinical translation potential of emerging biomarkers, including POLE/POLD1 mutations, immune score, circulating tumor DNA, and gut microbiome. Furthermore, it addresses the challenges in the clinical application of biomarkers, such as the controversy over TMB cutoff values and the heterogeneity of PD-L1 expression. Finally, it outlines future research directions with the aim of providing a basis for clinical decision-making in immunotherapy and facilitating the realization of precision medicine.
Insights
Immune checkpoint inhibitors (ICI) show promise for MSI-high colorectal cancer (CRC). New biomarkers are needed to guide ICI therapy selection and monitoring in MSS CRC patients for precision medicine.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immune checkpoint inhibitors (ICI) are effective for microsatellite instability-high (MSI-high) colorectal cancer (CRC).
- Monotherapy with ICI has limited efficacy in microsatellite stable (MSS) CRC.
- Combination immunotherapy regimens show potential for MSS CRC patients.
Purpose of the Study:
- To review traditional and emerging biomarkers for predicting ICI response in CRC.
- To explore the clinical translation potential of novel biomarkers.
- To address challenges in biomarker application for precision immunotherapy in CRC.
Main Methods:
- Review of current research on biomarkers for ICI therapy in CRC.
- Exploration of traditional biomarkers: tumor mutation burden (TMB) and PD-L1 expression.
- Investigation of emerging biomarkers: POLE/POLD1 mutations, immune score, circulating tumor DNA, and gut microbiome.
Main Results:
- TMB and PD-L1 expression are traditional biomarkers with limitations.
- Emerging biomarkers like POLE/POLD1 mutations, immune score, ctDNA, and gut microbiome show promise.
- Challenges include TMB cutoff controversies and PD-L1 expression heterogeneity.
Conclusions:
- Accurate biomarkers are crucial for selecting MSS CRC patients for ICI therapy.
- Dynamic monitoring of treatment efficacy requires robust biomarkers.
- Further research is needed to overcome clinical application challenges and advance precision medicine in CRC immunotherapy.
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