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Predictive biomarkers for immune checkpoint inhibition for patients with colorectal cancer: a comprehensive review
Ibrahim Halil Sahin1, Turcin Saridogan2, Richard Kim3
1Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Abstract:
Immune checkpoint inhibitors have resulted in treatment paradigm changes for the management of patients with solid tumors, including microsatellite instability-high (MSI-H) colorectal cancer (CRC). Although the benefit of these agents appears to be limited for microsatellite stable (MSS) CRC, recent studies suggest that the immune microenvironment of the early-stage MSS CRC and perhaps those with advanced-stage disease without active liver metastasis may be more immune permissive where relatively more promising responses were noted. At this time, biomarkers of immunotherapy for patients with CRC have not been well-defined. Except for the loss of mismatch repair protein (MMR) function and POLE/POLD1 mutations, most of the biomarkers of response are largely investigational. In this review article, we summarize recent research and drug development with immune checkpoint inhibitors for patients with MSS and MSI-H CRC and elaborate on investigational biomarkers, including but not limited to tumor mutation burden and immunoscore. We also discuss the relevance and potential applicability of these biomarkers to clinical practice for the use of immune checkpoint inhibitors and provided further perspective on future biomarker development.
Insights
Immune checkpoint inhibitors show promise in microsatellite instability-high colorectal cancer (CRC). Research explores their potential in microsatellite stable CRC and investigational biomarkers like tumor mutation burden for better treatment selection.
Area of Science:
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed solid tumor treatment, including microsatellite instability-high (MSI-H) colorectal cancer (CRC).
- Limited benefit from ICIs in microsatellite stable (MSS) CRC is observed, yet early-stage MSS CRC and select advanced cases show potential.
- Biomarkers for immunotherapy response in CRC are not well-defined, with few established markers beyond MMR deficiency and POLE/POLD1 mutations.
Purpose of the Study:
- To review current research and drug development of ICIs in both MSI-H and MSS CRC.
- To elaborate on investigational biomarkers for immunotherapy response in CRC.
- To discuss the clinical relevance and future development of biomarkers for CRC immunotherapy.
Main Methods:
- Literature review of recent studies on immune checkpoint inhibitors in colorectal cancer.
- Analysis of investigational biomarkers, including tumor mutation burden and immunoscore.
- Discussion of clinical applicability and future directions for biomarker development.
Main Results:
- ICIs are established treatments for MSI-H CRC.
- Emerging evidence suggests potential ICI efficacy in specific MSS CRC patient subsets.
- Tumor mutation burden and immunoscore are key investigational biomarkers.
Conclusions:
- Further research is needed to define optimal immunotherapy strategies for MSS CRC.
- Investigational biomarkers hold promise for personalizing ICI treatment in CRC.
- Development of robust biomarkers is crucial for advancing immunotherapy in colorectal cancer management.
