ArticleCancer immunology, immunotherapy : CII2012
Intratumoral interleukin-2/agonist CD40 antibody drives CD4+ -independent resolution of treated-tumors and CD4+ -dependent systemic and memory responses.
Article in Cancer immunology, immunotherapy : CII, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Stem-like T cells: molecular regulation, functional diversity, and therapeutic implications across diseases.Journal of translational medicine · 2025Review
- Therapeutic Immunomodulation of Tumor-Lymphatic Crosstalk via Intratumoral Immunotherapy.Molecular pharmaceutics · 2024Review
- Stem-like exhausted and memory CD8Nature reviews. Cancer · 2023Review
- Roles of CD4+ T cells as mediators of antitumor immunity.Frontiers in immunology · 2022Review
- The STING agonist, DMXAA, reduces tumor vessels and enhances mesothelioma tumor antigen presentation yet blunts cytotoxic T cell function in a murine model.Frontiers in immunology · 2022Article
- Intratumoural administration and tumour tissue targeting of cancer immunotherapies.Nature reviews. Clinical oncology · 2021Review
- Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines.Frontiers in pharmacology · 2021Review
- How the ageing microenvironment influences tumour progression.Nature reviews. Cancer · 2020Review
- Intratumoral administration of IL2- and TNF-based fusion proteins cures cancer without establishing protective immunity.Immunotherapy · 2018Article
- The Regulatory Status Adopted by Lymph Node Dendritic Cells and T Cells During Healthy Aging Is Maintained During Cancer and May Contribute to Reduced Responses to Immunotherapy.Frontiers in medicine · 2018Article
- Macrophage Depletion in Elderly Mice Improves Response to Tumor Immunotherapy, Increases Anti-tumor T Cell Activity and Reduces Treatment-Induced Cachexia.Frontiers in genetics · 2018Article
- Murine mesothelioma induces locally-proliferating IL-10(+)TNF-α(+)CD206(-)CX3CR1(+) M3 macrophages that can be selectively depleted by chemotherapy or immunotherapy.Oncoimmunology · 2016Article
- The efficacy of tumor debulking surgery is improved by adjuvant immunotherapy using imiquimod and anti-CD40.BMC cancer · 2014Article
- IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice.Age (Dordrecht, Netherlands) · 2014Article
- Enhanced therapeutic anti-tumor immunity induced by co-administration of 5-fluorouracil and adenovirus expressing CD40 ligand.Cancer immunology, immunotherapy : CII · 2014Article
- The "Trojan Horse" approach to tumor immunotherapy: targeting the tumor microenvironment.Journal of immunology research · 2014Review
- CD137 enhancement of HPV positive head and neck squamous cell carcinoma tumor clearance.Vaccines · 2014Article
- CD40 therapy and surgery: a potential immunologic partnership.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2013Article
- Turning the tumor microenvironment into a self vaccine site.Oncoimmunology · 2012Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting interleukin-2 (IL-2) and/or agonist anti-CD40 antibody (Ab) into tumors represents an effective vaccination strategy that avoids systemic toxicity and resolves treated-site tumors. Here, we examined IL-2 and/or anti-CD40 Ab-driven local versus systemic T cell function and the installation of T cell memory. Single tumor studies showed that IL-2 induced a potent CD4+ and CD8+ T cell response that was limited to the draining lymph node and treated-site tumor, and lymph node tumor-specific CD8+ T cells did not upregulate CD44. A two-tumor model showed that while IL-2-treated-site tumors resolved, distal tumors continued to grow, implying limited systemic immunity. In contrast, anti-CD40 Ab treatment with or without IL-2 expanded the systemic T cell response to non-draining lymph nodes, and distal tumors resolved. Tumor-specific T cells in lymph nodes of anti-CD40 Ab ± IL-2-treated mice upregulated CD44, demonstrating activation and transition to effector/memory migratory cells. While CD40-activated CD4+ T cells were not required for eradicating treated-site tumors, they, plus CD8+ T cells, were crucial for removing distal tumors. Rechallenge/depletion experiments showed that the effector/memory phase required the presence of previously CD40/IL-2-activated CD4+ and CD8+ T cells to prevent recurrence. These novel findings show that different T cell effector mechanisms can operate for the eradication of local treated-site tumors versus untreated distal tumors and that signaling through CD40 generates a whole of body, effector/memory CD4+ and CD8+ T cell response that is amplified and prolonged via IL-2. Thus, successful immunotherapy needs to generate collaborating CD4+ and CD8+ T cells for a complete long-term protective cure.
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What OpenQuestion holds
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.