PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

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Summary

Immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis have brought significant clinical benefit in many solid cancer types, including gastrointestinal malignancies. However, it has been estimated that only 20-40% of patients respond to treatment. The pattern of expression and potential predictive value of PD-L1 as an immunohistochemical biomarker has been extensively studied in gastrointestinal neoplasms. Until now, its predictive value has been demonstrated, and is currently in use only in upper gastrointestinal malignancies (gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma).

In this Review, we describe the technical aspects and challenges related to PD-L1 immunohistochemical assays, the current role of PD-L1 as a biomarker in clinical practice and we outline the main studies and clinical trials analyzing the prognostic and predictive value of PD-L1 in gastrointestinal cancers.

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Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade.

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Is Open Access

Comprehensive molecular characterization of gastric adenocarcinoma

Adam J. Bass, Vesteinn Thorsson, Ilya Shmulevich … (2015)

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

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Author and article information

Journal

Journal ID (nlm-ta): Pathologica

Journal ID (iso-abbrev): Pathologica

Journal ID (publisher-id): PATHOL

Title: Pathologica

Publisher: Pacini Editore srl

ISSN (Print): 0031-2983

ISSN (Electronic): 1591-951X

Publication date (Electronic): 01 October 2022

Publication date Collection: October 2022

Volume: 114

Issue: 5

Pages: 352-364

Affiliations

[1 ] IRCCS Ospedale Policlinico San Martino , Genoa, Italy

[2 ] Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova , Italy

[3 ] Unit of Pathology, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza , San Giovanni Rotondo, FG, Italy

[4 ] Department of Pathology, Centro Hospitalar Universitário de São João (CHUSJ) , Porto, Portugal

[5 ] Department of Pathology, Faculty of Medicine of the University of Porto (FMUP) , Portugal

[6 ] i3S - Instituto de Investigação e Inovação em Saúde da Universidade do Porto , Portugal

[7 ] Public Healthcare Trust of the Autonomous Province of Trento, Santa Chiara Hospital , Department of Laboratory Medicine, Pathology Unit, Trento, Italy

[8 ] Department of Medicine (DIMED), Surgical Pathology Unit, University Hospital of Padua , Padua (PD), Italy

[9 ] Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, and IRCCS San Matteo Hospital , Pavia, Italy

[10 ] Veneto Institute of Oncology IOV - IRCCS , Padua (PD), Italy

Author notes

Correspondence Matteo Fassan Department of Medicine (DIMED); Surgical Pathology & Cytopathology Unit; University of Padua, via Gabelli 61, 35121 Padua, Italy Tel.: (+39) 049 8211312 E-mail: matteo.fassan@ 123456unipd.it

^* Equally contributed as first author

Article

DOI: 10.32074/1591-951X-803

PMC ID: 9614301

PubMed ID: 36305021

SO-VID: 4bc3dc05-0cdb-45bd-836d-e79e5493d87f

License:

This is an open access journal distributed in accordance with the CC-BY-NC-ND (Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International) license: the work can be used by mentioning the author and the license, but only for non-commercial purposes and only in the original version. For further information: https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en

History

Date received : 20 September 2022

Date accepted : 20 September 2022

Page count

Figures: 2, Tables: 1, Equations: 0, References: 100, Pages: 13

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PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

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Most cited references 97

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.

Immunity, inflammation, and cancer.

Comprehensive molecular characterization of gastric adenocarcinoma

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