New insights into the role of complement system in colorectal cancer - Review

Sep 23, 2026

Colorectal cancer (CRC) is among the most common cancers worldwide, and immune regulation has increasingly highlighted the complement system as a key regulator of tumor immunity. Complement cascades and their activation products—generated via cascade-dependent and cascade-independent routes—connect complement activity with tumor-associated inflammation. Complement components, activation products, regulatory proteins, and complement receptors contribute to tumor cell growth and shaping of the tumor microenvironment. This review summarizes CRC tumor immunity roles and emphasizes unconventional cascade-independent pathways in CRC progression, suggesting mechanistic understanding in colitis-associated CRC may support prevention, target identification, and treatment development for CAC.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Complement system and its roles in CRC

Clinical significance of complement system in CRC

Conclusions and prospects

MOLECULAR MEDICINE REPORTS 31: 68, 2025 New insights into the role of complement system in colorectal cancer (Review) YUWEN XU, JIAQI ZHOU, YUANYUAN WU, JIE SHEN, XIAOYAN FU, MEIFANG LIU* and SHUJUAN LIANG* Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China Received September 21, 2024; Accepted December 23, 2024 DOI: 10. 3892/mmr.2025.13433 Abstract. Colorectal cancer (CRC) is one of the most common cancers worldwide. With the growing understanding of immune regulation in tumors, the complement system has been recognized as a key regulator of tumor immunity. Traditionally, the complement cascade, considered an evolu‑ tionarily conserved defense mechanism against invading pathogens, has been viewed as a crucial inhibitor of tumor progression. Complement components or activation products produced via cascade‑dependent or ‑independent processes are associated with the regulation of tumor‑associated inflam‑ mation . Various forms of complement activation products present in body fluids or inside cells, along with complement regulatory proteins and complement receptors, are involved in tumor cell growth and modulating the tumor microenviron‑ ment. In the present review, the role of the complement system in the tumor immunity of CRC is discussed. In addition, the contribution of the unconventional cascade‑independent pathway of complement activation in CRC progression is high‑ lighted. A deeper understanding of the mechanism underlying the complement system in colitis‑associated colorectal cancer (CAC) may provide novel insights to assist the development of methods to prevent tumor progression and identify potential targets for the treatment of CAC. Correspondence to: Professor Meifang Liu or Professor Shujuan Liang, Key Laboratory of Immune Microment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, 7166 Baotong West Street, Weifang, Shandong 261053, P.R. China E‑mail: [lmf00719@163.com](lmf00719@163.com) E‑mail: [liangshj@sdsmu.edu.cn](liangshj@sdsmu.edu.cn) *Contributed equally Key words: complement, colorectal cancer, tumor immunity, cascade‑independent, intracellular activation Contents 1. Introduction 2. Complement system and its roles in CRC 3. Clinical significance of complement system in CRC 4. Conclusions and prospects 1. Introduction The complement system comprises several soluble and membrane‑bound proteins that, when activated, provide a congenital defense against microbial infection . In addition to its defensive role, complement activation elicits numerous biological effects, including leukocyte recruitment, smooth muscle contraction and increased vascular permeability (1‑4) . Although the activation of the complement system is strictly regulated by various regulators and inhibitors in the body fluidsand plasma (5,6), inappropriate or uncontrolled activation of the complement system can lead to local or systemic inflam‑ mation, tissue damage and disease (7,8) . A number of studies have provided novel insights into the structure and function of complement proteins, which have improved our understanding of how different components of the complement system participate in the destruction or restoration of homeostasis in the tumor microenvironment (TME) . This increased knowl‑ edge has inspired novel approaches for complement‑targeted therapy (9,10) . Colorectal cancer (CRC) is one of the most frequently occurring cancers worldwide, ranking third among all cancersin incidence and second in terms of mortality (11) . Despite certain improvements that have been made to treatment regimens, including surgery, radiotherapy and chemotherapy, the mortality rate of CRC remains high (12) . Notably, thera‑ pies targeting the immune system

FAQs

Why is the complement system considered important in colorectal cancer?

The complement system is recognized as a key regulator of tumor immunity, linking complement activation and immune regulation to colorectal cancer progression within the tumor microenvironment.

How do complement activation products influence CRC?

Complement components and activation products, produced through cascade-dependent or cascade-independent processes, are involved in regulating tumor-associated inflammation, tumor cell growth, and modulation of the tumor microenvironment.

What is the focus on unconventional cascade-independent pathways?

The review highlights how an unconventional cascade-independent activation pathway of complement contributes to CRC progression, and discusses its potential mechanistic value for colitis-associated colorectal cancer.

Sep 23, 2026

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