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The Role of Immune Checkpoint Inhibitors in Colorectal Adenocarcinoma

Daniel R Almquist1, Daniel H Ahn1, Tanios S Bekaii-Saab2

  • 1Division of Hematology and Medical Oncology, Mayo Clinic Cancer Center, Mayo Clinic Hospital, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA.

Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
|April 5, 2020
PubMed

Insights

Immune checkpoint inhibitors (ICIs) show promise in microsatellite instability-high colorectal cancer but not in microsatellite-stable colorectal cancer. Research is exploring immune strategies to overcome ICI resistance in MSS/pMMR CRC.

Area of Science:

  • Oncology
  • Immunology
  • Gastroenterology

Background:

  • Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) are FDA-approved for microsatellite instability-high/DNA mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC).
  • These ICIs demonstrate significant antitumor activity in MSI-H/dMMR CRC, establishing their role in treatment.
  • However, microsatellite-stable/DNA mismatch repair-proficient (MSS/pMMR) CRC, comprising 95% of metastatic cases, does not respond to current ICI therapy.

Purpose of the Study:

  • To review current clinical data on ICI efficacy in colorectal cancer.
  • To explore emerging immune-based strategies for overcoming ICI resistance in MSS/pMMR CRC.
  • To identify potential therapeutic avenues for MSS/pMMR CRC patients who do not benefit from ICIs.

Main Methods:

  • Review of available clinical trial data concerning ICI therapy in colorectal cancer.
  • Analysis of research on the mechanisms of immune evasion in MSS/pMMR CRC.
  • Synthesis of emerging immune-based strategies aimed at enhancing ICI effectiveness.

Main Results:

  • ICIs are effective in MSI-H/dMMR CRC but lack efficacy in MSS/pMMR CRC.
  • Understanding the interaction between the immune system and MSS/pMMR CRC cells is crucial.
  • Novel immune-based strategies are under investigation to improve treatment outcomes.

Conclusions:

  • There is a critical need for effective treatments for MSS/pMMR CRC.
  • Further research into immune-based strategies is essential to overcome ICI resistance.
  • Developing new therapies for MSS/pMMR CRC will expand treatment options for the majority of CRC patients.

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