Anti-integrin αvβ6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis

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Abstract

Background

No specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvβ6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis.

Methods

Serum anti-integrin αvβ6 autoantibody levels were compared between 26 patients with ICI-induced colitis and 157 controls. Endoscopic images of ICI-induced colitis were centrally reviewed. Characteristics of anti-integrin αvβ6 autoantibodies in the ICI-induced colitis patients were compared with those of UC patients.

Results

Anti-integrin αvβ6 autoantibodies were found in 8/26 (30.8%) patients with ICI-induced colitis and 3/157 (1.9%) controls ( P < 0.001). Patients with anti-integrin αvβ6 autoantibodies had significantly more typical UC endoscopic features than those without the autoantibodies ( P < 0.001). Anti-integrin αvβ6 autoantibodies in ICI-induced colitis patients were associated with grade ≥3 colitis ( P = 0.001) and steroid resistance ( P = 0.005). Anti-integrin αvβ6 autoantibody titers correlated with ICI-induced colitis disease activity. Anti-integrin αvβ6 autoantibodies of ICI-induced colitis exhibited similar characteristics to those of UC.

Conclusions

Anti-integrin αvβ6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis.

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Most cited references 29

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Cancer immunotherapy using checkpoint blockade

Jedd Wolchok, Antoni Ribas (2018)

The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte antigen-4 (CTLA-4) or the programmed death-1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the pre-existence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long lasting disease control, yet one third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon gamma signaling pathways. New generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.

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Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance

Filipe C Martins, Latifyan Sofiya, Gerasimos Sykiotis … (2019)

Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.

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Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders.

Fernando Magro, Paolo Gionchetti, Rami Eliakim … (2017)

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Author and article information

Contributors

Masahiro Shiokawa:

ORCID: http://orcid.org/0000-0001-6436-3888

machan@kuhp.kyoto-u.ac.jp

Hisato Kawakami:

ORCID: http://orcid.org/0000-0002-3280-4850

kawakami_h@med.kindai.ac.jp

Journal

Journal ID (nlm-ta): Br J Cancer

Journal ID (iso-abbrev): Br J Cancer

Title: British Journal of Cancer

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 0007-0920

ISSN (Electronic): 1532-1827

Publication date (Electronic): 9 March 2024

Publication date PMC-release: 9 March 2024

Publication date (Print): 18 May 2024

Volume: 130

Issue: 9

Pages: 1552-1560

Affiliations

[1 ]Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, ( https://ror.org/02kpeqv85) Kyoto, Japan

[2 ]Department of Medical Oncology, Kindai University Faculty of Medicine, ( https://ror.org/05kt9ap64) Osaka, Japan

[3 ]Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, ( https://ror.org/02kpeqv85) Kyoto, Japan

[4 ]Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, ( https://ror.org/03tgsfw79) Hyogo, Japan

[5 ]Department of Gastroenterology and Hepatology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, ( https://ror.org/05rsbck92) Osaka, Japan

[6 ]Department of Gastroenterology, Shizuoka General Hospital, ( https://ror.org/0457h8c53) Shizuoka, Japan

[7 ]GRID grid.414973.c, Department of Gastroenterology and Hepatology, , Kansai Electric Power Hospital, ; Osaka, Japan

Author information

Masataka Yokode http://orcid.org/0000-0003-0751-0188

Masahiro Shiokawa http://orcid.org/0000-0001-6436-3888

Hisato Kawakami http://orcid.org/0000-0002-3280-4850

Nobuyuki Kakiuchi http://orcid.org/0000-0003-4893-5414

Hidetoshi Hayashi http://orcid.org/0000-0001-8787-5587

Article

Publisher ID: 2647

DOI: 10.1038/s41416-024-02647-1

PMC ID: 11058246

PubMed ID: 38461170

SO-VID: afc51376-c2ef-456e-a512-a96460aa8d4d

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 25 October 2023

Date revision received : 25 February 2024

Date accepted : 27 February 2024

Funding

Funded by: the Japanese Society of Gastroenterology

Funded by: FundRef https://doi.org/10.13039/501100001691, MEXT | Japan Society for the Promotion of Science (JSPS);

Award ID: 22J14815

Award Recipient : Masataka Yokode

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: diagnostic markers,autoimmunity

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: diagnostic markers, autoimmunity

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Anti-integrin αvβ6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis

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Karger: Oncology

Most cited references 29

Cancer immunotherapy using checkpoint blockade

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance

Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders.

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