Immunotherapy in colorectal cancer

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• The immune tumor microenvironment (TME) significantly influences colorectal cancer (CRC) progression and therapeutic response.
• Immune cell profiling of the TME offers prognostic and predictive insights for CRC patients.
• Immunotherapy, particularly targeting immune checkpoints like PD-1 and CTLA-4, has transformed CRC treatment, especially for microsatellite instability-high (MSI-H) subtypes.

Purpose of the Study:

• To explore the role of the immune TME in colorectal cancer (CRC) and its impact on therapeutic interventions.
• To understand the prognostic and predictive value of immune cell characterization in CRC.
• To identify factors influencing immunotherapy efficacy and resistance in CRC, particularly in microsatellite stable (MSS) and immunotherapy-resistant MSI-H cancers.

Main Methods:

• Analysis of immune cell populations within the tumor microenvironment of colorectal cancer (CRC).
• Evaluation of molecular and cellular characteristics of CRC.
• Review of clinical data on immunotherapy response in MSI-H and MSS CRC, including PD-1 and CTLA-4 inhibitors.

Main Results:

• Immunotherapy, including PD-1 inhibitors, is highly effective in MSI-H CRC due to high immune infiltration and neoantigen load.
• A PD-1 inhibitor is now approved for MSS CRC with high tumor mutation burden.
• The anti-tumor activity of immunotherapy remains limited in the majority of CRC cases, highlighting a need for improved strategies.

Conclusions:

• Immune characterization of CRC provides prognostic value but has not yet translated into widespread therapeutic interventions for all subtypes.
• Further research is crucial to delineate factors predicting immunotherapy efficacy and resistance.
• Identifying novel therapeutic targets and combination strategies is essential for improving outcomes in MSS CRC and immunotherapy-resistant MSI-H CRC.