ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 65 citations in OpenAlex.
- Combination Nivolumab, CD137 Agonism, and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- 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
- Immunologic determinants of infusion products and the tumor microenvironment govern response to TIL therapy in advanced melanoma.Med (New York, N.Y.) · 2026Article
- Dual stimulation of CD40 and 41BB pathways during ex-vivo TIL expansion enhances CD8+ T cell expansion.bioRxiv : the preprint server for biology · 2026Article
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Tumor infiltration therapy: from FDA approval to next-generation approaches.Clinical and experimental medicine · 2025Review
- Clinical and Fundamental Research Progressions on Tumor-Infiltrating Lymphocytes Therapy in Cancer.Vaccines · 2025Review
- Application of adoptive cell therapy in malignant melanoma.Journal of translational medicine · 2025Review
- Tumour-infiltrating lymphocyte therapy landscape: prospects and challenges.BMJ oncology · 2025Review
- Tumour-infiltrating lymphocyte therapy for patients with advanced-stage melanoma.Nature reviews. Clinical oncology · 2024Review
- Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances.Frontiers in immunology · 2024Review
- Neoantigen-specific CD4Journal for immunotherapy of cancer · 2023Article
- An iPSC-derived exosome-pulsed dendritic cell vaccine boosts antitumor immunity in melanoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Fucosylation of HLA-DRB1 regulates CD4Nature cancer · 2023Article
- Article
- Adoptive tumor infiltrating lymphocytes cell therapy for cervical cancer.Human vaccines & immunotherapeutics · 2022Review
- Tumor Infiltrating Lymphocyte (TIL) Therapy for Solid Tumor Treatment: Progressions and Challenges.Cancers · 2022Review
- Therapeutic approaches targeting CD95L/CD95 signaling in cancer and autoimmune diseases.Cell death & disease · 2022Review
- Isolation and Maintenance of Tumor-Infiltrating Lymphocytes for Translational and Clinical Applications: Established Methods and New Developments.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Signal pathways of melanoma and targeted therapy.Signal transduction and targeted therapy · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCultured tumor fragments from melanoma metastases have been used for years as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy (ACT). The expansion of tumor-reactive CD8(+) T cells with interleukin-2 (IL2) in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8(+) T cells recently found to constitute the majority of tumor-specific T cells. EXPERIMENTAL
designWe used an agonistic anti-4-1BB antibody added during the initial tumor fragment cultures to provide in situ 4-1BB costimulation.
resultsWe found that addition of an agonistic anti-4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8(+) TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFκB activation and the induction of T-cell survival and memory genes, as well as enhanced IL2 responsiveness, in the CD8(+) T cells in the fragments and emerging from the fragments. Early provision of 4-1BB costimulation also affected the dendritic cells (DC) by activating NFκB in DC and promoting their maturation inside the tumor fragments. Blocking HLA class I prevented the enhanced outgrowth of CD8(+) T cells with anti-4-1BB, suggesting that an ongoing HLA class I-mediated antigen presentation in early tumor fragment cultures plays a role in mediating tumor-specific CD8(+) TIL outgrowth.
conclusionsOur results highlight a previously unrecognized concept in TIL ACT that the tumor microenvironment can be dynamically regulated in the initial tumor fragment cultures to regulate the types of T cells expanded and their functional characteristics.
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.