Research ArticlesClinical Significance of Program Death Ligand-1 and Indoleamine-2,3-Dioxygenase Expression in Colorectal CarcinomaHacking, Sean MB, BCh, BAO; Vitkovski, Taisia DO; Jain, Swachi MBBS; Jin, Cao MD, PhD; Chavarria, Hector MD; Wu, Dongling MD; Nasim, Mansoor MD, PhDAuthor Information Department of Pathology and Laboratory Medicine, Zucker School of Medicine at Hofstra Northwell, Hempstead, NY M.N. and S.H.: developed the theoretical formalism. S.H., C.J., and H.C.: performed the analytic calculations and performed the numerical simulations. S.H., T.V., and M.N.: contributed to the final version of the manuscript. S.H., D.W., S.J., H.C., C.J., and T.V.: contributed to the acquisition and analysis of data. The authors declare no conflict of interest. Reprints: Sean Hacking, MB, BCh, BAO, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11042 (e-mail: [email protected]). Applied Immunohistochemistry & Molecular Morphology: March 2021 - Volume 29 - Issue 3 - p 201-208 doi: 10.1097/PAI.0000000000000868 Buy Metrics 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.