ArticleCancer discovery2016
Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression.
Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- The single nucleotide polymorphisms of interleukin-10 are associated with the risk of leukaemia: Evidence from 18 case-control studies.Medicine · 2020Pooled it
- The influence of a single hemodialysis procedure on human T lymphocytes.Scientific reports · 2019Trial
- Tumor-targeted IL-10 synergizes with IL-2 to enhance antitumor immunity while minimizing immune-related adverse events.Nature communications · 2026Article
- Liposomes in tumor treatment: a double-edged sword.Science China. Life sciences · 2026Review
- A High-Fiber, Plant-Based Diet in Myeloma Precursor Disorders: Results from the NUTRIVENTION Clinical Trial and Preclinical Vk*MYC Model.Cancer discovery · 2026Article
- C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.iScience · 2026Review
- Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026Review
- The complement system contributes to the immunosuppressive microenvironment of uveal melanoma.Journal of translational medicine · 2026Article
- Immune Predictors of Radiotherapy Outcomes in Cervical Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Understanding the role of C5a/C5aR1-mediated complement activation pathway in tumor progression and therapy resistance.Science China. Life sciences · 2026Review
- The insider's perspective: The intracellular complosome and immune cell dynamics in cancer.Clinical and translational medicine · 2026Review
- Review
- The Pleiotropic Effect of Complement C5a-C5aR1 Pathway in Diseases: From Immune Regulation to Targeted Therapy.International journal of molecular sciences · 2025Review
- Complement C3 in panvascular disease: a central integrator of immune signaling and vascular remodeling.Clinical science (London, England : 1979) · 2025Review
- Review
- The complement system in intestinal inflammation and cancer.The Journal of clinical investigation · 2025Review
- Chrysoeriol Chemosensitized Renal Cell Carcinoma (RCC) Cell Lines to Trigger TRAIL Induced Apoptosis In Vitro by Up-Regulating Pro-Apoptotic and Down-Regulating Anti-Apoptotic Genetic Factors.Food science & nutrition · 2025Article
- The complement system and kidney cancer: pathogenesis to clinical applications.The Journal of clinical investigation · 2025Review
- IL-10-Directed Cancer Immunotherapy: Preclinical Advances, Clinical Insights, and Future Perspectives.Cancers · 2025Review
- Interactions Between the Innate and Adaptive Immune Responses.Advances in experimental medicine and biology · 2025Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledIn contrast to its inhibitory effects on many cells, IL10 activates CD8(+) tumor-infiltrating lymphocytes (TIL) and enhances their antitumor activity. However, CD8(+) TILs do not routinely express IL10, as autocrine complement C3 inhibits IL10 production through complement receptors C3aR and C5aR. CD8(+) TILs from C3-deficient mice, however, express IL10 and exhibit enhanced effector function. C3-deficient mice are resistant to tumor development in a T-cell- and IL10-dependent manner; human TILs expanded with IL2 plus IL10 increase the killing of primary tumors in vitro compared with IL2-treated TILs. Complement-mediated inhibition of antitumor immunity is independent of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint pathway. Our findings suggest that complement receptors C3aR and C5aR expressed on CD8(+) TILs represent a novel class of immune checkpoints that could be targeted for tumor immunotherapy. Moreover, incorporation of IL10 in the expansion of TILs and in gene-engineered T cells for adoptive cell therapy enhances their antitumor efficacy. SIGNIFICANCE: Our data suggest novel strategies to enhance immunotherapies: a combined blockade of complement signaling by antagonists to C3aR, C5aR, and anti-PD-1 to enhance anti-PD-1 efficacy; a targeted IL10 delivery to CD8(+) TILs using anti-PD-1-IL10 or anti-CTLA4-IL10 fusion proteins; and the addition of IL10 in TIL expansion for adoptive cellular therapy. Cancer Discov; 6(9); 1022-35. ©2016 AACR.See related commentary by Peng et al., p. 953This article is highlighted in the In This Issue feature, p. 932.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.