ArticleJournal of immunotherapy (Hagerstown, Md. : 1997)2011
Costimulation through the CD137/4-1BB pathway protects human melanoma tumor-infiltrating lymphocytes from activation-induced cell death and enhances antitumor effector function.
Article in Journal of immunotherapy (Hagerstown, Md. : 1997), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 135 citations in OpenAlex.
- Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer.The Journal of clinical investigation · 2014Trial
- Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2012Trial
- Utilizing T-cell Activation Signals 1, 2, and 3 for Tumor-infiltrating Lymphocytes (TIL) Expansion: The Advantage Over the Sole Use of Interleukin-2 in Cutaneous and Uveal Melanoma.Journal of immunotherapy (Hagerstown, Md. : 1997)Trial
- OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Selective expansion of T-cell receptor engineered T cells with increased stem-like phenotypes using neoantigen stimulation.Journal for immunotherapy of cancer · 2025Article
- Bulk and Single-Cell Transcriptomes Reveal Exhausted Signature in Prognosis of Hepatocellular Carcinoma.Genes · 2025Article
- Advances and prospects in tumor infiltrating lymphocyte therapy.Discover oncology · 2024Review
- Pharmacologic HIF stabilization activates costimulatory receptor expression to increase antitumor efficacy of adoptive T cell therapy.Science advances · 2024Article
- Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes.Journal for immunotherapy of cancer · 2024Article
- Batf3Cell reports · 2024Article
- Biomarkers for response to TIL therapy: a comprehensive review.Journal for immunotherapy of cancer · 2024Review
- Engaging stimulatory immune checkpoint interactions in the tumour immune microenvironment of primary liver cancers - how to push the gas after having released the brake.Frontiers in immunology · 2024Review
- XFab-α4-1BB/CD40L fusion protein activates dendritic cells, improves expansion of antigen-specific T cells, and exhibits antitumour efficacy in multiple solid tumour models.Cancer immunology, immunotherapy : CII · 2023Article
- CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects.Science advances · 2023Article
- Targeting Co-Stimulatory Receptors of the TNF Superfamily for Cancer Immunotherapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Signaling via a CD28/CD40 chimeric costimulatory antigen receptor (CoStAR™), targeting folate receptor alpha, enhances T cell activity and augments tumor reactivity of tumor infiltrating lymphocytes.Frontiers in immunology · 2023Article
- Targeting T cell checkpoints 41BB and LAG3 and myeloid cell CXCR1/CXCR2 results in antitumor immunity and durable response in pancreatic cancer.Nature cancer · 2023Article
- Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies.Journal for immunotherapy of cancer · 2022Article
- Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment.Cancers · 2021Review
18 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
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) with high-dose interleukin-2 is a promising form of immunotherapy for stage IV melanoma having clinical response rates of 50% or more. One of the major problems preventing further success of this therapy is that the current protocols used to highly expand TIL for infusion drive CD8(+) T cells to differentiate into effector cells losing key costimulatory molecules such as CD28 and CD27. This has been associated with a lack of persistence in vivo for reasons not entirely clear. In this study, we demonstrate that while human melanoma CD8(+) TIL lost CD27 and CD28 expression during the rapid expansion for ACT, they gained expression of the alternative costimulatory molecule CD137/4-1BB, and to a lesser extent CD134/OX40. Postrapid expansion protocol (REP) TIL were found to be highly sensitive to activation-induced cell death when reactivated through the T-cell receptor with low levels of OKT3 antibody. However, coligation of 4-1BB using 2 different agonistic anti-4-1BB antibodies potently prevented activation-induced cell death of post-REP CD8(+) TIL, including those specific for melanoma antigen recognized by T cells, and facilitated even further cell expansion. This was correlated with increased levels of bcl-2 and bcl-xL together with decreased bim expression. 4-1BB costimulated post-REP TIL also expressed increased levels of the cytolytic granule proteins and exhibited enhanced cytotoxic T-cell activity against melanoma cells. Lastly, post-REP CD8(+) TIL were protected from cell death by anti-4-1BB ligation when exposed to human leukocyte antigen-matched melanoma cells. Our results indicate that 4-1BB costimulation may significantly improve TIL survival during melanoma ACT and boost antitumor cytolytic activity.
Indexed as
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.