ArticleThe Journal of clinical investigation2011
IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 149 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Intravital Microscopy (IVM) in Patients With Peritoneal Carcinomatosis (PC)
Intravital Microscopy (IVM) in Human Solid Tumors
Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 226 citations in OpenAlex.
- Cancer therapy with iron oxide nanoparticles: Agents of thermal and immune therapies.Advanced drug delivery reviews · 2020Pooled it
- A Pilot Study of Stereotactic Body Radiation Therapy Combined with Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- CD8⁺ T Cell infiltration and spatial organization in cancer: mechanisms, barriers, and therapeutic strategies.Molecular biomedicine · 2026Review
- IL-6/IL-6R-Mediated Mechanisms in Lung Cancer: From Pathogenesis to Potential Therapeutic Targets.Immunology · 2026Review
- Remodeling the Immune Landscape: How Obesity-Induced SASPs Create a Pro-Tumorigenic Niche.Current obesity reports · 2026Review
- Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Sex parity in stimulation of murine lymphocyte trafficking in response to fever-range systemic thermal therapy.International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 2025Article
- Dual implication of endothelial adhesion molecules in tumor progression and cancer immunity.Cell adhesion & migration · 2025Review
- Doxorubicin loaded polylactide nanoparticles functionalized histamine promote apoptosis of human gastric cancer cells AGS.Scientific reports · 2025Article
- Cell-intrinsic PD-L1 signaling drives immunosuppression by myeloid-derived suppressor cells through IL-6/Jak/Stat3 in PD-L1-high lung cancer.Journal for immunotherapy of cancer · 2025Article
- From cold to hot: mechanisms of hyperthermia in modulating tumor immunology for enhanced immunotherapy.Frontiers in immunology · 2025Review
- The antitumor activity of TGFβ-specific T cells is dependent on IL-6 signaling.Cellular & molecular immunology · 2025Article
- Emerging Mechanisms of Physical Exercise Benefits in Adjuvant and Neoadjuvant Cancer Immunotherapy.Biomedicines · 2024Review
- SubvertingBiology · 2024Review
- PHF8/KDM7B: A Versatile Histone Demethylase and Epigenetic Modifier in Nervous System Disease and Cancers.Epigenomes · 2024Review
- Locoregional therapies combined with immune checkpoint inhibitors for liver metastases.Cancer cell international · 2024Review
- LAG-3 : recent developments in combinational therapies in cancer.Cancer science · 2024Review
- AI-2 quorum sensing controlled delivery of cytolysin-A by tryptophan auxotrophic low-endotoxic Salmonella and its anticancer effects in CT26 mice with colon cancer.Journal of advanced research · 2024Article
- Immunomodulatory and Anticancer Effects ofPharmaceutics · 2024Article
- Mechanisms Underlying the Rarity of Skeletal Muscle Cancers.International journal of molecular sciences · 2024Review
89 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Immune cells are key regulators of neoplastic progression, which is often mediated through their release of cytokines. Inflammatory cytokines such as IL-6 exert tumor-promoting activities by driving growth and survival of neoplastic cells. However, whether these cytokines also have a role in recruiting mediators of adaptive anticancer immunity has not been investigated. Here, we report that homeostatic trafficking of tumor-reactive CD8+ T cells across microvascular checkpoints is limited in tumors despite the presence of inflammatory cytokines. Intravital imaging in tumor-bearing mice revealed that systemic thermal therapy (core temperature elevated to 39.5°C ± 0.5°C for 6 hours) activated an IL-6 trans-signaling program in the tumor blood vessels that modified the vasculature such that it could support enhanced trafficking of CD8+ effector/memory T cells (Tems) into tumors. A concomitant decrease in tumor infiltration by Tregs during systemic thermal therapy resulted in substantial enhancement of Tem/Treg ratios. Mechanistically, IL-6 produced by nonhematopoietic stromal cells acted cooperatively with soluble IL-6 receptor-α and thermally induced gp130 to promote E/P-selectin- and ICAM-1-dependent extravasation of cytotoxic T cells in tumors. Parallel increases in vascular adhesion were induced by IL-6/soluble IL-6 receptor-α fusion protein in mouse tumors and patient tumor explants. Finally, a causal link was established between IL-6-dependent licensing of tumor vessels for Tem trafficking and apoptosis of tumor targets. These findings suggest that the unique IL-6-rich tumor microenvironment can be exploited to create a therapeutic window to boost T cell-mediated antitumor immunity and immunotherapy.
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Identifiers
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.