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Cancer-related inflammation is a crucial component of the tumor microenvironment (TME). Complement activation occurs in cancer and supports the development of an inflammatory microenvironment. Complement has traditionally been considered a mechanism of immune resistance against cancer, and its activation is known to contribute to the cytolytic effects of antibody-based immunotherapeutic treatments. However, several studies have recently revealed that complement activation may exert protumoral functions by sustaining cancer-related inflammation and immunosuppression through different molecular mechanisms, targeting both the TME and cancer cells. These new discoveries have revealed that complement manipulation can be considered a new strategy for cancer therapies. Here we summarize our current understanding of the mechanisms by which the different elements of the complement system exert antitumor or protumor functions, both in preclinical studies and in human tumorigenesis. Complement components can serve as disease biomarkers for cancer stratification and prognosis and be exploited for tumor treatment.
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http://dx.doi.org/10.1158/2326-6066.CIR-23-0399 | DOI Listing |
Liver Int
October 2025
Division of Gastroenterology and Hepatology, Department of Medicine, The Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research & Cold Spring Harbor Laboratory, Northwell Health, Manhasset, New York, USA.
Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths, primarily due to late-stage diagnosis. In this multicenter study, our goal is to identify functional biomarkers that stratify the risk of HCC in patients with cirrhosis (CP) for early diagnosis.
Methods: Five thousand and eight serum proteins (Somascan) were analysed in Cohort A (477 CP, including 125 HCC).
Front Immunol
September 2025
Department of Urology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, China.
In the study of prostate diseases, the microenvironment associated with chronic prostatitis is characterized by abnormal activation of immune cells, leading to excessive accumulation of pro-inflammatory factors and an imbalance in the antioxidant defense system. This results in the overproduction of reactive oxygen species (ROS) and the subsequent triggering of oxidative stress. Oxidative stress persistently disrupts the homeostasis of prostate tissue through various mechanisms, including the damage to biomacromolecules, the regulation of inflammatory pathways, and the induction of apoptosis.
View Article and Find Full Text PDFCarcinogenesis
September 2025
Department of Medicine, Gastroenterology and Hepatology Division, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611-3010, USA.
Esophageal cancer is a major cause of cancer-related death, often preceded with chronic inflammation and injuries. The NFκB/IKKβ pathway plays a central role in inflammation, yet its role in early esophageal carcinogenesis remains unclear. This study investigated the role of epithelial IKKβ in early esophageal carcinogenesis.
View Article and Find Full Text PDFEnviron Int
September 2025
Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address:
Background: Although per- and polyfluoroalkyl substances (PFAS) have been linked to chronic liver diseases, the specific cellular and molecular mechanisms by which different PFAS contribute to human liver dysfunction remain unclear. This study aims to elucidate those mechanisms.
Methods: We exposed a multi-donor human liver spheroid model composed of multiple cell types to 20 µM of PFHxS, PFOA, PFOS, or PFNA for seven days, followed by single-cell RNA sequencing and lipid staining.
Eur J Immunol
September 2025
IRCCS Humanitas Research Hospital, Milan, Italy.
IL-1 family members and their signaling receptors are key drivers of inflammation in sterile or infectious conditions, as well as polarization of the innate and adaptive immunity. Deregulated or excessive activation of the IL-1 system is associated with detrimental inflammatory reactions. Beside signaling receptors, IL-1-family receptors comprise decoy or negative regulatory receptors, which regulate cell activation mediated by IL-1 family ligands.
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