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Immune checkpoint blockade in microsatellite instable colorectal cancers: Back to the clinic

Franck Housseau1, Nicolas J Llosa1

  • 1Department of Oncology; Sidney Kimmel Comprehensive Cancer Center; Johns Hopkins University ; Baltimore, MD, USA.

Oncoimmunology
|July 9, 2015
PubMed

Insights

Microsatellite Instable colorectal cancer (CRC) has an active immune environment but is hindered by immune checkpoints. Defective mismatch repair may identify CRC patients who will benefit from checkpoint inhibitor therapy.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Microsatellite Instable (MSI) colorectal cancer (CRC) exhibits an active Th1/CTL immune microenvironment.
  • This active immune response is counterbalanced by the upregulation of immune checkpoint proteins.

Purpose of the Study:

  • To investigate the potential of defective mismatch repair as a biomarker for selecting CRC patients for immunotherapy.
  • To evaluate the hypothesis that MSI status predicts response to immune checkpoint inhibitors.

Main Methods:

  • Analysis of the immune microenvironment in MSI colorectal cancer.
  • Assessment of immune checkpoint expression in relation to mismatch repair status.

Main Results:

  • An active Th1/CTL immune microenvironment was observed in MSI CRC.
  • Upregulated expression of multiple immune checkpoints was identified, counterbalancing the immune activity.

Conclusions:

  • Defective mismatch repair may serve as a predictive biomarker for immunotherapy in colorectal cancer.
  • Clinical trials are underway to validate the efficacy of checkpoint inhibitors in patients identified by this biomarker.

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