ArticleThe EMBO journal2024
Acidity suppresses CD8 + T-cell function by perturbing IL-2, mTORC1, and c-Myc signaling.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed.
- A 'three-axis synergy' immunotherapeutic strategy for malignant bone tumors based on natural bioactives and bioactive materials.Bioactive materials · 2026Review
- pH-neutralization strategy to suppress GPCR68 spatiotemporally activates T cells and enhances anti-tumor immunity.Bioactive materials · 2026Article
- Research progress on precision targeted therapy strategies for breast cancer based on tumor microenvironment.iScience · 2026Review
- Circadian engineering of in vivo CAR T cell therapy for precision oncology.NPJ precision oncology · 2026Review
- Longitudinal Monitoring of Metabolic Gradients in Microreactor Culture Platforms by Raman Spectroscopy.Biosensors · 2026Article
- CAR-T cell therapies are coming after glioblastoma: An overview of early phase clinical trials and future perspectives.iScience · 2026Review
- Reprogramming the tumor immune microenvironment in cervical cancer: synergy between radiotherapy and immunotherapy.Molecular cancer · 2026Review
- The dysadherin/carbonic anhydrase 9 axis shapes an acidic tumor microenvironment to promote colorectal cancer progression.Signal transduction and targeted therapy · 2026Article
- Lethality is local, but survival is systemic: Temporal and multi-organ responses to chlorine gas exposure in a murine model.Current research in toxicology · 2026Article
- Tumor-driven stabilization of CD8Frontiers in immunology · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- Generation and Characterization of CAR-T Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The interplay of dietary sugar, chronic inflammation, and bladder cancer: mechanistic insights, evidence, and prevention strategies.Frontiers in immunology · 2026Review
- Transdermal bicarbonate buffer therapy increases intratumoral pH and elicits antitumor responses in bladder cancer.Frontiers in immunology · 2026Article
- The symbiotic axis between the acidic tumor microenvironment and cancer stem cells: a driver of malignancy and therapeutic resistance.Frontiers in oncology · 2026Review
- A Hidden Checkpoint: Bidirectional pH Remodeling of the Immunological Synapse in Cancer, Methods, and Therapeutic Opportunities.Journal of immunology research · 2026Review
- Low pH, High Stakes: A Narrative Review Exploring the Acid-Sensing GPR65 Pathway as a Novel Approach in Renal Cell Carcinoma.Cancers · 2025Review
- Review
- Roles of endothelial cells during infection.Current opinion in immunology · 2025Review
- Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency.Cancer cell · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
CD8 + T cells have critical roles in tumor control, but a range of factors in their microenvironment such as low pH can suppress their function. Here, we demonstrate that acidity restricts T-cell expansion mainly through impairing IL-2 responsiveness, lowers cytokine secretion upon re-activation, and reduces the cytolytic capacity of CD8 + T cells expressing low-affinity TCR. We further find decreased mTORC1 signaling activity and c-Myc levels at low pH. Mechanistically, nuclear/cytoplasmic acidification is linked to mTORC1 suppression in a Rheb-, Akt/TSC2/PRAS40-, GATOR1- and Lkb1/AMPK-independent manner, while c-Myc levels drop due to both decreased transcription and higher levels of proteasome-mediated degradation. In addition, lower intracellular levels of glutamine, glutamate, and aspartate, as well as elevated proline levels are observed with no apparent impact on mTORC1 signaling or c-Myc levels. Overall, we suggest that, due to the broad impact of acidity on CD8 + T cells, multiple interventions will be required to restore T-cell function unless intracellular pH is effectively controlled.
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.