American Association for Cancer Research
Browse
15417786mcr170735-sup-193560_2_supp_4567182_p4493d.docx (27.54 kB)

Supplementary Table S3 from Landscape of Tumor Mutation Load, Mismatch Repair Deficiency, and PD-L1 Expression in a Large Patient Cohort of Gastrointestinal Cancers

Download (27.54 kB)
journal contribution
posted on 2023-04-03, 17:27 authored by Mohamed E. Salem, Alberto Puccini, Axel Grothey, Derek Raghavan, Richard M. Goldberg, Joanne Xiu, W. Michael Korn, Benjamin A. Weinberg, Jimmy J. Hwang, Anthony F. Shields, John L. Marshall, Philip A. Philip, Heinz-Josef Lenz

Published immune checkpoint inhibitor (ICI) response rate in gastrointestinal cancers.

History

ARTICLE ABSTRACT

The efficacy of immunotherapy varies widely among different gastrointestinal cancers. Response to immune checkpoint inhibitors is shown to correlate with tumor mutation load (TML), mismatch repair deficiency (dMMR) status, and programmed cell death-ligand 1 (PD-L1) expression. Herein, we quantify TML, dMMR, and PD-L1 expression and determine their interrelationship in gastrointestinal cancers. Here, a total of 4,125 tumors from 14 different gastrointestinal cancer sites were studied using validated assays. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor specimens using the NextSeq platform. TML was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Microsatellite instability (MSI) was assessed using direct analysis of altered known MSI loci in the target regions of the sequenced genes. PD-L1 expression was analyzed by IHC. Interestingly, right-sided colon and small-bowel adenocarcinomas had the highest prevalence of TML-high tumors (14.6% and 10.2%, respectively). Pancreatic neuroendocrine tumors and gastrointestinal stromal tumors had the lowest rates of TML-high (1.3% and 0%, respectively). TML-high was strongly associated with MSI-H (P < 0.0001). However, all TML-high anal cancers (8.3%) were microsatellite stable (MSS). Higher PD-L1 expression was more likely to be seen in MSI compared with MSS tumors (20.6% vs. 7.8%, P < 0.0001).Implications: TML-high rate varied widely among gastrointestinal cancers. Although MSI is conceivably the main driver for TML-high, other factors may be involved. Future clinical trials are needed to evaluate whether the integration of TML, MSI, and PD-L1 could better identify potential responders to immunotherapy. Mol Cancer Res; 16(5); 805–12. ©2018 AACR.

Usage metrics

    Molecular Cancer Research

    Categories

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC