Roles of TIR domain-containing adaptor protein in tumor - Inflammation and immune regulation via toll-like receptor signaling

Sep 22, 2026

This narrative review critically synthesizes evidence on the roles of TIR domain-containing adaptor protein (TIRAP) in tumorigenesis and cancer progression, emphasizing inflammatory and immune regulatory mechanisms driven by toll-like receptor signaling. A targeted search of studies from 2015–2024 was conducted using PubMed and Web of Science, with foundational 1998–2014 publications added by reference tracking. Findings link TIRAP to malignant progression in bladder, pancreatic, and gastric cancers through the TLR2/4-MyD88-NF-κB/MAPK axis and an immunosuppressive tumor microenvironment, while colorectal effects may be homeostatic and protective. Regulation depends on cellular origin, ligand specificity, and epigenetic modifications such as promoter methylation, highlighting TIRAP as a biomarker and therapeutic target.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

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Abstract

Introduction

Discovery and cellular localization of TIR domain-containing adaptor protein (TIRAP)

Role of TLR signaling in tumorigenesis

Rationale and objectives

Roles of TIR domain-containing adaptor protein in tumor: Inﬂammation and immune regulation via toll-like receptor signaling Journal of International Medical Research 2026, Vol. 54(8) 1–14 © The Author(s) 2026 Article reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions)[ ](sagepub.com/journals-permissions)[DOI: 10.1177/03000605261472952](DOI: 10.1177/03000605261472952)[ ](DOI: 10.1177/03000605261472952)[journals.sagepub.com/home/imr](journals.sagepub.com/home/imr) Huihui Jiang 1, Rui Zhang2, Shanshan Ding3, Zhen Yu3, Chenrui Qi4, Jin Meng4 and Lu Wang 1,3 Abstract This narrative review aimed to critically synthesize and evaluate the current evidence on the roles of TIR domaincontaining adaptor protein in tumorigenesis and cancer progression, with a particular focus on elucidating the underlying inﬂammatory and immune regulatory mechanisms mediated by toll-like receptor signaling. A targeted literature search of recent studies (2015–2024) was performed using PubMed and Web of Science. Classic foundational publications (1998– 2014) were supplemented through reference tracking. We included experimental, cellular, and clinical studies focusing on TIR domain-containing adaptor protein in cancer. The synthesized ﬁndings indicate that TIR domain-containing adaptor protein has been implicated in malignant progression in bladder, pancreatic, and gastric cancers by sustaining chronic inﬂammation and shaping an immunosuppressive tumor microenvironment through the TLR2/4-MyD88-NF-κB/MAPK axis, whereas it may exert homeostatic and protective effects in colorectal cancer. TIR domain-containing adaptor protein activity is tightly regulated by cellular origin, ligand speciﬁcity, and epigenetic modiﬁcations such as promoter methylation, which are closely associated with cancer risk and disease severity. TIR domain-containing adaptor protein serves asa critical regulator in inﬂammation-driven tumors with distinct context-dependent functions and represents a promising biomarker and therapeutic target. Further research focusing on its precise regulatory mechanisms and cell-speciﬁc targeted strategies will facilitate its clinical translation. Keywords TIR domain-containing adaptor protein, toll-like receptor signaling, tumor, inﬂammation, tumor immune microenvironment Received: 5 February 2026; revised: 9 June 2026; accepted: 8 July 2026 Introduction Discovery and cellular localization of TIR domain-containing adaptor protein (TIRAP) TIRAP (also known as MyD88 adaptor-like protein (MAL)) is a key intracellular adaptor protein in the toll-like receptor (TLR) signaling pathway.1–3 It functions as a critical bridge linking pathogen recognition to downstream inﬂammatory 1 School of Pharmacy, Shandong Second Medical University, China 2Department of Pharmacy, Jinan Mental Health Center, China 3Department of Pharmacy, Central Hospital Afﬁliated to Shandong First Medical University, China 4School of pharmacy, Shandong First Medical University, China Corresponding author: Lu Wang, School of Pharmacy, Shandong Second Medical University, 261053, Weifang, Shandong, China. Email: [lulucc@163.com](lulucc@163.com) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as speciﬁed on the SAGE and Open Access page ([https://us](https://us). [sagepub.com/en-us/nam/open-access-at-sage](sagepub.com/en-us/nam/open-access-at-sage)). responses.3 TIRAP participates in signaling mediated by cell-surface TLR2/4 as well as endosomal TLR7/9 .4,5 Dysregulation of TIRAP expression or function is closely implicated in the development of multiple malignant tumors.6,7 Role of T

FAQs

What is the main focus of this review?

The review critically evaluates how TIR domain-containing adaptor protein (TIRAP) contributes to tumor development and progression, with emphasis on inflammatory and immune regulation mediated by toll-like receptor signaling.

How was the literature search conducted?

Studies from 2015 to 2024 were targeted using PubMed and Web of Science, and classic foundational publications from 1998 to 2014 were added via reference tracking.

What mechanism links TIRAP to malignant progression in certain cancers?

The findings associate TIRAP with chronic inflammation and an immunosuppressive tumor microenvironment through the TLR2/4-MyD88-NF-κB/MAPK axis, especially in bladder, pancreatic, and gastric cancers.

Sep 22, 2026

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