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Clinical Significance of Program Death Ligand-1 and Indoleamine-2,3-Dioxygenase Expression in Colorectal Carcinoma

Clinical Significance of Program Death Ligand-1 and Indoleamine-2,3-Dioxygenase Expression in... Colorectal cancer is a heterogenous disease with striking biological diversity. Colorectal carcinoma (CRC) is one of the most common malignancies, accounting for over 9% of all cancers worldwide. To put it in perspective, 5% of people will develop CRC in their lifetime. Biomarkers specific to a particular cancer type can assist in the evaluation of survival probability and help clinicians assess treatment modalities, an example being programmed death ligand-1 (PD-L1). With regards to PD-L1, this is the first study to evaluate the SP-142 antibody clone in CRC. The Ventana PD-L1 (SP-142) assay for PD-L1 expression identifies patients who may benefit from treatment with atezolizumab. SP-142 was chosen as large stage 3 clinical trials are being undertaken with atezolizumab in CRC. Indoleamine 2,3-dioxygenase (IDO-1) was also chosen as there are several ongoing trials for Epacadostat, the best-in-class oral IDO-1 enzyme inhibitor, in many solid tumors. For solid tumors, IDO-1-based immune escape has the potential to inhibit monotherapeutic efficacy of PD-L1-based therapeutics. In this study, a total of 223 cases of CRC were retrospectively reviewed and clinicopathologic data were analyzed in relation to PD-L1 and IDO-1 protein expression. Moreover, tumor-infiltrating lymphocytes, mismatch repair deficiency, high mitotic index, and worse survival outcomes were found in cohorts with significant PD-L1 and IDO-1 expression. Both PD-L1 and IDO-1 are actionable biomarkers, with potential therapeutic implications in CRC. Our findings support the theoretical foundation for targeting PD-L1 and IDO-1 in CRC, which now needs verification in well-designed robust clinical trials. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied Immunohistochemistry & Molecular Morphology Wolters Kluwer Health

Clinical Significance of Program Death Ligand-1 and Indoleamine-2,3-Dioxygenase Expression in Colorectal Carcinoma

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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
ISSN
1541-2016
DOI
10.1097/pai.0000000000000868
Publisher site
See Article on Publisher Site

Abstract

Colorectal cancer is a heterogenous disease with striking biological diversity. Colorectal carcinoma (CRC) is one of the most common malignancies, accounting for over 9% of all cancers worldwide. To put it in perspective, 5% of people will develop CRC in their lifetime. Biomarkers specific to a particular cancer type can assist in the evaluation of survival probability and help clinicians assess treatment modalities, an example being programmed death ligand-1 (PD-L1). With regards to PD-L1, this is the first study to evaluate the SP-142 antibody clone in CRC. The Ventana PD-L1 (SP-142) assay for PD-L1 expression identifies patients who may benefit from treatment with atezolizumab. SP-142 was chosen as large stage 3 clinical trials are being undertaken with atezolizumab in CRC. Indoleamine 2,3-dioxygenase (IDO-1) was also chosen as there are several ongoing trials for Epacadostat, the best-in-class oral IDO-1 enzyme inhibitor, in many solid tumors. For solid tumors, IDO-1-based immune escape has the potential to inhibit monotherapeutic efficacy of PD-L1-based therapeutics. In this study, a total of 223 cases of CRC were retrospectively reviewed and clinicopathologic data were analyzed in relation to PD-L1 and IDO-1 protein expression. Moreover, tumor-infiltrating lymphocytes, mismatch repair deficiency, high mitotic index, and worse survival outcomes were found in cohorts with significant PD-L1 and IDO-1 expression. Both PD-L1 and IDO-1 are actionable biomarkers, with potential therapeutic implications in CRC. Our findings support the theoretical foundation for targeting PD-L1 and IDO-1 in CRC, which now needs verification in well-designed robust clinical trials.

Journal

Applied Immunohistochemistry & Molecular Morphology – Wolters Kluwer Health

Published: Mar 24, 2021

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