ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Immunotherapy Expands and Maintains the Function of High-Affinity Tumor-Infiltrating CD8 T Cells In Situ.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Microbial-derived immunostimulatory small molecule augments anti-PD-1 therapy in lung cancer.Cell reports. Medicine · 2026Article
- uPAR expression in M-MDSCs under high LDHA activity in pancreatic ductal adenocarcinoma.Scientific reports · 2025Article
- Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer.Cancer discovery · 2025Article
- OX40/OX40L: a new target for tumor immunotherapy and its clinical research progress.Frontiers in oncology · 2025Review
- An HIV-1 CRISPR-Cas9 membrane trafficking screen reveals a role for PICALM intersecting endolysosomes and immunity.iScience · 2024Article
- Tumor resident memory CD8 T cells and concomitant tumor immunity develop independently of CD4 help.Scientific reports · 2023Article
- Reconciling intrinsic properties of activating TNF receptors by native ligands versus synthetic agonists.Frontiers in immunology · 2023Review
- Late-stage MC38 tumours recapitulate features of human colorectal cancer - implications for appropriate timepoint selection in preclinical studies.Frontiers in immunology · 2023Article
- Combined analysis of T cell activation and T cell-mediated cytotoxicity by imaging cytometry.Journal of immunological methods · 2022Article
- Article
- Combining bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) improves systemic antitumor CD8Journal for immunotherapy of cancer · 2022Article
- A Phase I, Open-Label, Dose-Escalation Study of the OX40 Agonist Ivuxolimab in Patients with Locally Advanced or Metastatic Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- AHCCFrontiers in immunology · 2022Article
- Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells.Nature communications · 2021Article
- The Dynamic Entropy of Tumor Immune Infiltrates: The Impact of Recirculation, Antigen-Specific Interactions, and Retention on T Cells in Tumors.Frontiers in oncology · 2021Review
- Anti-neoplastic and immunomodulatory potency of co-treatment based on bovine lactoferrin and/or muramyl dipeptide in tumor-bearing mice.Toxicology research · 2020Article
- New pathways in immune stimulation: targeting OX40.ESMO open · 2020Article
- Potentiating the Antitumor Activity of Cytotoxic T CellsFrontiers in immunology · 2020Article
- Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies.Science translational medicine · 2019Article
- Immune targets in the tumor microenvironment treated by radiotherapy.Theranostics · 2019Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cancer cells harbor high-affinity tumor-associated Ags capable of eliciting potent antitumor T cell responses, yet detecting these polyclonal T cells is challenging. Therefore, surrogate markers of T cell activation such as CD69, CD44, and programmed death-1 (PD-1) have been used. We report in this study that in mice, expression of activation markers including PD-1 is insufficient in the tumor microenvironment to identify tumor Ag-specific T cells. Using the Nur77GFP T cell affinity reporter mouse, we highlight that PD-1 expression can be induced independent of TCR ligation within the tumor. Given this, we characterized the utility of the Nur77GFP model system in elucidating mechanisms of action of immunotherapies independent of PD-1 expression. Coexpression of Nur77GFP and OX40 identifies a polyclonal population of high-affinity tumor-associated Ag-specific CD8(+) T cells, which produce more IFN-γ in situ than OX40 negative and doubles in quantity with anti-OX40 and anti-CTLA4 mAb therapy but not with anti-PD-1 or programmed death ligand-1. Moreover, expansion of these high-affinity CD8 T cells prolongs survival of tumor-bearing animals. Upon chronic stimulation in tumors and after adoptive cell therapy, CD8 TCR signaling and Nur77GFP induction is impaired, and tumors progress. However, this can be reversed and overall survival significantly enhanced after adoptive cell therapy with agonist OX40 immunotherapy. Therefore, we propose that OX40 agonist immunotherapy can maintain functional TCR signaling of chronically stimulated tumor-resident CD8 T cells, thereby increasing the frequency of cytotoxic, high-affinity, tumor-associated Ag-specific cells.
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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.