ArticlePloS one2014
Bystander activation and anti-tumor effects of CD8+ T cells following Interleukin-2 based immunotherapy is independent of CD4+ T cell help.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Radiotherapy enhances natural killer cell cytotoxicity and localization in pre-clinical canine sarcomas and first-in-dog clinical trial.Journal for immunotherapy of cancer · 2017Trial
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- The expression of PD-L1 on tumor-derived exosomes enhances infiltration and anti-tumor activity of αCD3 × αPD-L1 bispecific antibody-armed T cells.Cancer immunology, immunotherapy : CII · 2024Article
- Machine learning identifies the role of SMAD6 in the prognosis and drug susceptibility in bladder cancer.Journal of cancer research and clinical oncology · 2024Article
- Bystander activated CD8Nature communications · 2024Article
- Survival and division fate programs are preserved but retuned during the naïve to memory CD8Immunology and cell biology · 2024Article
- CD40 ligand stimulation affects the number and memory phenotypes of human peripheral CD8BMC immunology · 2023Article
- Technology meets TILs: Deciphering T cell function in the -omics era.Cancer cell · 2023Review
- Combining bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) improves systemic antitumor CD8Journal for immunotherapy of cancer · 2022Article
- The Ugly Duckling Turned to Swan: A Change in Perception of Bystander-Activated Memory CD8 T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Review
- Expansion of an Unusual Virtual Memory CD8Frontiers in immunology · 2021Article
- Solid Tumor Microenvironment Can Harbor and Support Functional Properties of Memory T Cells.Frontiers in immunology · 2021Article
- Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment.Frontiers in immunology · 2021Review
- Severe Human Lassa Fever Is Characterized by Nonspecific T-Cell Activation and Lymphocyte Homing to Inflamed Tissues.Journal of virology · 2020Article
- Article
- Molecular and metabolic pathways mediating curative treatment of a non-Hodgkin B cell lymphoma by Sindbis viral vectors and anti-4-1BB monoclonal antibody.Journal for immunotherapy of cancer · 2019Article
- Bystander T Cells: A Balancing Act of Friends and Foes.Trends in immunology · 2018Review
- Tumor-Localized Secretion of Soluble PD1 Enhances Oncolytic Virotherapy.Cancer research · 2017Article
- Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy.Journal for immunotherapy of cancer · 2017Article
- CD4+ T cell-mediated cytotoxicity eliminates primary tumor cells in metastatic melanoma through high MHC class II expression and can be enhanced by inhibitory receptor blockade.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
We have previously demonstrated that immunotherapy combining agonistic anti-CD40 and IL-2 (IT) results in synergistic anti-tumor effects. IT induces expansion of highly cytolytic, antigen-independent "bystander-activated" (CD8(+)CD44high) T cells displaying a CD25(-)NKG2D(+) phenotype in a cytokine dependent manner, which were responsible for the anti-tumor effects. While much attention has focused on CD4(+) T cell help for antigen-specific CD8(+) T cell expansion, little is known regarding the role of CD4(+) T cells in antigen-nonspecific bystander-memory CD8(+) T cell expansion. Utilizing CD4 deficient mouse models, we observed a significant expansion of bystander-memory T cells following IT which was similar to the non-CD4 depleted mice. Expanded bystander-memory CD8(+) T cells upregulated PD-1 in the absence of CD4(+) T cells which has been published as a hallmark of exhaustion and dysfunction in helpless CD8(+) T cells. Interestingly, compared to CD8(+) T cells from CD4 replete hosts, these bystander expanded cells displayed comparable (or enhanced) cytokine production, lytic ability, and in vivo anti-tumor effects suggesting no functional impairment or exhaustion and were enriched in an effector phenotype. There was no acceleration of the post-IT contraction phase of the bystander memory CD8(+) response in CD4-depleted mice. The response was independent of IL-21 signaling. These results suggest that, in contrast to antigen-specific CD8(+) T cell expansion, CD4(+) T cell help is not necessary for expansion and activation of antigen-nonspecific bystander-memory CD8(+) T cells following IT, but may play a role in regulating conversion of these cells from a central memory to effector phenotype. Additionally, the expression of PD-1 in this model appears to be a marker of effector function and not exhaustion.
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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.