Genotypic and phenotypic signatures to predict immune checkpoint blockade therapy response in patients with colorectal cancer

Xianda Zhao, Audre May, Emil Lou, Subbaya Subramanian

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Immune checkpoint blockade therapy (ICBT) has resulted in extended overall survival for some patients with certain types of cancer, most prominently including colorectal cancer (CRC) associated with microsatellite instability (MSI). However, most patients with CRC whose phenotypes have microsatellite stability (MSS) are unresponsive to ICBT. In efforts to understand the responsiveness of CRC tumors to ICBT, genotypic and phenotypic signatures of CRC tumors are now being investigated. The MSI and MSS classification has been clinically validated as helpful in predicting response vs nonresponse to ICBT in patients with CRC. Other potential predictive markers include mutational and neoantigen loads, T-cell receptor diversity, and the immune score system, all of which have mechanistic connections to ICBT response. These novel predictive signatures could provide unprecedented insights into patients with CRC associated with MSS. Clinical trials or prospective cohort studies using standardized methodologies for biomarker quantification should be illuminating. Further validation of these novel predictive signatures will be essential to tailoring treatment of patients whose CRC is most likely to respond to ICBT.

Original languageEnglish (US)
Pages (from-to)62-70
Number of pages9
JournalTranslational Research
Volume196
DOIs
StatePublished - Jun 1 2018

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Microsatellite Repeats
Colorectal Neoplasms
Tumors
Microsatellite Instability
Therapeutics
Immune system
Biomarkers
T-Cell Antigen Receptor
Immune System
Cohort Studies
Clinical Trials
Prospective Studies
Phenotype
Survival

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

Cite this

Genotypic and phenotypic signatures to predict immune checkpoint blockade therapy response in patients with colorectal cancer. / Zhao, Xianda; May, Audre; Lou, Emil; Subramanian, Subbaya.

In: Translational Research, Vol. 196, 01.06.2018, p. 62-70.

Research output: Contribution to journalReview article

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abstract = "Immune checkpoint blockade therapy (ICBT) has resulted in extended overall survival for some patients with certain types of cancer, most prominently including colorectal cancer (CRC) associated with microsatellite instability (MSI). However, most patients with CRC whose phenotypes have microsatellite stability (MSS) are unresponsive to ICBT. In efforts to understand the responsiveness of CRC tumors to ICBT, genotypic and phenotypic signatures of CRC tumors are now being investigated. The MSI and MSS classification has been clinically validated as helpful in predicting response vs nonresponse to ICBT in patients with CRC. Other potential predictive markers include mutational and neoantigen loads, T-cell receptor diversity, and the immune score system, all of which have mechanistic connections to ICBT response. These novel predictive signatures could provide unprecedented insights into patients with CRC associated with MSS. Clinical trials or prospective cohort studies using standardized methodologies for biomarker quantification should be illuminating. Further validation of these novel predictive signatures will be essential to tailoring treatment of patients whose CRC is most likely to respond to ICBT.",
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