ReviewFrontiers in immunology2016
Starved and Asphyxiated: How Can CD8(+) T Cells within a Tumor Microenvironment Prevent Tumor Progression.
Review in Frontiers in immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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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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.
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Who cites it
60 citing papers in PubMed, 103 citations in OpenAlex.
- Dendritic cell vaccines targeting tumor blood vessel antigens in combination with dasatinib induce therapeutic immune responses in patients with checkpoint-refractory advanced melanoma.Journal for immunotherapy of cancer · 2021Trial
- Immunogenic cell death: synergizing ferroptosis and cuproptosis to overcome immunotherapy resistance.Medical oncology (Northwood, London, England) · 2026Review
- The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.Translational lung cancer research · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- Metabolic reprogramming through PIM3 inhibition reverses hypoxia-induced CAR-T cell dysfunction in solid tumors.Journal of translational medicine · 2025Article
- Interactions between ferroptosis and tumour development mechanisms: Implications for gynaecological cancer therapy (Review).Oncology reports · 2025Review
- Significant Advancements and Evolutions in Chimeric Antigen Receptor Design.International journal of molecular sciences · 2024Review
- The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Review
- Human colorectal cancer: upregulation of the adaptor protein Rai in TILs leads to cell dysfunction by sustaining GSK-3 activation and PD-1 expression.Cancer immunology, immunotherapy : CII · 2024Article
- Tumor ABCC4-mediated release of PGE2 induces CD8International journal of biological sciences · 2024Article
- Metformin improves cancer immunotherapy by directly rescuing tumor-infiltrating CD8 T lymphocytes from hypoxia-induced immunosuppression.Journal for immunotherapy of cancer · 2023Article
- VSSP-activated macrophages mediate senescence and tumor inhibition in a preclinical model of advanced prostate cancer.Cell communication and signaling : CCS · 2023Article
- Identification of gene signatures related to hypoxia and angiogenesis in pancreatic cancer to aid immunotherapy and prognosis.Frontiers in oncology · 2023Article
- Article
- Tumor Budding Is an Independent Prognostic Factor in Pancreatic Adenocarcinoma and It Positively Correlates with PD-L1 Expression on Tumor Cells.Biomedicines · 2022Article
- Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.Cell communication and signaling : CCS · 2022Review
- Hypoxia Is a Dominant Remodeler of the Effector T Cell Surface Proteome Relative to Activation and Regulatory T Cell Suppression.Molecular & cellular proteomics : MCP · 2022Article
- Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier.Cancer cell international · 2022Review
- CD8Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Although cancer immunotherapy has achieved significant breakthroughs in recent years, its overall efficacy remains limited in the majority of patients. One major barrier is exhaustion of tumor antigen-specific CD8(+) tumor-infiltrating lymphocytes (TILs), which conventionally has been attributed to persistent stimulation with antigen within the tumor microenvironment (TME). A series of recent studies have highlighted that the TME poses significant metabolic challenges to TILs, which may contribute to their functional exhaustion. Hypoxia increases the expression of coinhibitors on activated CD8(+) T cells, which in general reduces the T cells' effector functions. It also impairs the cells' ability to gain energy through oxidative phosphorylation. Glucose limitation increases the expression of programed cell death protein-1 and reduces functions of activated CD8(+) T cells. A combination of hypoxia and hypoglycemia, as is common in solid tumors, places CD8(+) TILs at dual metabolic jeopardy by affecting both major pathways of energy production. Recently, a number of studies addressed the effects of metabolic stress on modulating CD8(+) T cell metabolism, differentiation, and functions. Here, we discuss recent findings on how different types of metabolic stress within the TME shape the tumor-killing capacity of CD8(+) T cells. We propose that manipulating the metabolism of TILs to more efficiently utilize nutrients, especially during intermittent periods of hypoxia could maximize their performance, prolong their survival and improve the efficacy of active cancer immunotherapy.
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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.