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A Blueprint to Advance Colorectal Cancer Immunotherapies
Dung T Le1, Vanessa M Hubbard-Lucey2, Michael A Morse3
1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
Cancer Immunology Research
|October 18, 2017
Summary
Colorectal cancer (CRC) remains resistant to immunotherapy. Research aims to improve immunotherapy for microsatellite stable (MSS) CRC by understanding T-cell responses and identifying predictive biomarkers.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Immunotherapy is a standard cancer treatment, but colorectal cancer (CRC) shows resistance.
- Defective mismatch repair (microsatellite instability-high) CRC responds to immunotherapy, unlike the microsatellite stable (MSS) majority.
- This highlights the need for novel immunotherapies for MSS CRC.
Purpose of the Study:
- To compile research, identify gaps, and create a blueprint for advancing immunotherapy in colorectal cancer.
- To explore reasons for immunotherapy resistance in MSS CRC.
- To propose a research framework for improving immunotherapy in CRC.
Main Methods:
- Convened experts in CRC and immunotherapy.
- Reviewed ongoing research efforts.
- Identified gaps in translational and clinical research.
Main Results:
- Lack of a T-cell inflamed phenotype is a potential reason for checkpoint blockade failure in MSS CRC.
- Mechanisms of T-cell infiltration, activation, and suppression in MSS CRC are unclear.
- The predictive value of biomarkers like immunoscores and IFN signatures for MSS CRC immunotherapy is unknown.
Conclusions:
- Further research is needed to understand and overcome immunotherapy resistance in MSS CRC.
- Biomarkers are crucial for predicting immunotherapy response and guiding treatment strategies.
- A framework is proposed to identify immunologic factors for improved CRC immunotherapy, aiming for integration into routine care.