ArticleJournal for immunotherapy of cancer2021
Complement C3a and C5a receptor blockade modulates regulatory T cell conversion in head and neck cancer.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Targeting regulatory T cells in the prostate cancer microenvironment: From mechanisms to therapeutics (Review).Molecular medicine reports · 2026Review
- Local, but not circulating, complement C3 shapes immune checkpoint blockade efficacy by controlling myeloid cell infiltration.Nature communications · 2026Article
- Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Understanding the role of C5a/C5aR1-mediated complement activation pathway in tumor progression and therapy resistance.Science China. Life sciences · 2026Review
- Subtype- and race-specific variations in the immune landscape of breast cancer: therapeutic implications.NPJ breast cancer · 2025Article
- Verteporfin-Mediated In Situ Nanovaccine Based on Local Conventional-Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Role of the oral-gut microbiota axis in pancreatic cancer: a new perspective on tumor pathophysiology, diagnosis, and treatment.Molecular medicine (Cambridge, Mass.) · 2025Review
- The role of the complement system in the response to cytotoxic therapy.Seminars in immunology · 2025Review
- The role of the tumor microenvironment in HNSCC resistance and targeted therapy.Frontiers in immunology · 2025Review
- The Past and Future of Inflammation as a Target to Cancer Prevention.Cancer prevention research (Philadelphia, Pa.) · 2024Article
- The role of the C5a-C5aR pathway in iron metabolism and gastric cancer progression.Frontiers in immunology · 2024Article
- METTL3-mediated m6A methylation of C1qA regulates the Rituximab resistance of diffuse large B-cell lymphoma cells.Cell death discovery · 2023Article
- Radiomics Features on Magnetic Resonance Images Can Predict C5aR1 Expression Levels and Prognosis in High-Grade Glioma.Cancers · 2023Article
- The impact of inflammation and acute phase activation in cancer cachexia.Frontiers in immunology · 2023Review
- Comprehensive Pan-Cancer Analyses of Immunogenic Cell Death as a Biomarker in Predicting Prognosis and Therapeutic Response.Cancers · 2022Article
- The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis.Nature communications · 2022Article
- Complement C5 is a novel biomarker for liver metastasis of colorectal cancer.Journal of gastrointestinal oncology · 2022Article
- The mouse oral carcinoma (MOC) model: A 10-year retrospective on model development and head and neck cancer investigations.Oral oncology · 2022Review
- C3aR costimulation enhances the antitumor efficacy of CAR-T cell therapy through Th17 expansion and memory T cell induction.Journal of hematology & oncology · 2022Article
- Proteome and phosphoproteome signatures of recurrence for HPVCommunications medicine · 2022Article
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Authors and funding
13 authors.
Funding
Abstract
backgroundResistance to therapy is a major problem in treating head and neck squamous cell carcinomas (HNSCC). Complement system inhibition has been shown to reduce tumor growth, metastasis, and therapeutic resistance in other tumor models, but has yet to be explored in the context of HNSCC. Here, we tested the effects of complement inhibition and its therapeutic potential in HNSCC.
methodsWe conducted our studies using two Human Papilloma Virus (HPV)-negative HNSCC orthotopic mouse models. Complement C3aR and C5aR1 receptor antagonists were paired with radiation therapy (RT). Tumor growth was measured and immune populations from tumor, lymph node, and peripheral blood were compared among various treatment groups. Genetically engineered mouse models
resultsIn contrast to established literature, inhibition of complement C3a and C5a signaling using receptor antagonists accelerated tumor growth in multiple HNSCC cell lines and corresponded with increased frequency of regulatory T cell (Treg) populations. Local C3a and C5a signaling has importance for CD4 T cell homeostasis and eventual development into effector phenotypes. Interruption of this signaling axis drives a phenotypic conversion of CD4
conclusionsOur data establish Tregs as a pro-tumorigenic driver during complement inhibition and provide evidence that targeted C3a and C5a receptor inhibition may add therapeutic advantage when coupled with anti-Treg therapy.
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