ArticleImmunity2023
TCR signaling promotes formation of an STS1-Cbl-b complex with pH-sensitive phosphatase activity that suppresses T cell function in acidic environments.
Article in Immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 24 citations in OpenAlex.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- LAG3 checkpoint function and its mechanism of action in therapeutic targeting.Nature reviews. Immunology · 2026Review
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- SLC4A7/NBCn1 maintains intracellular pH to support mTORC1 activity and antibody-secreting cell differentiation.Nature communications · 2026Article
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- Daphnetin prevents acute graft-versus-host disease by suppressing donor T cell expansion and function.Inflammopharmacology · 2026Article
- Kupffer cell calibration of T cell responses via VSIG4-CD5 interaction promotes tumor evasion.Nature immunology · 2026Article
- Suppressor of TCR signaling 2 (Sts-2) as a potential immunotherapy target and prognostic biomarker in cervical cancer.Journal of gynecologic oncology · 2026Article
- Mitophagy-driven multidimensional regulation of tumor immune evasion and context-dependent therapeutic strategies.Journal of translational medicine · 2026Review
- The impact of concomitant medications on treatment outcomes in patients with cancer receiving immune checkpoint inhibitors.Nature reviews. Cancer · 2026Review
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Post-translational modifications in CD8Frontiers in immunology · 2026Review
- Different tumour-resident memory T-cell subsets regulate responses to anti-PD-1 and anti-CTLA-4 cancer immunotherapies.Nature communications · 2025Article
- STS2 deficiency revives CD8Journal for immunotherapy of cancer · 2025Article
- Cbl-b inhibitor NX-1607 activates MAPK/ERK signaling pathway and enhances T-cell activation.Journal for immunotherapy of cancer · 2025Article
- Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer.Nature reviews. Drug discovery · 2025Review
- Roles of TULA-family proteins in T cells and autoimmune diseases.Genes and immunity · 2025Review
- Exploring the impact of antibody-dependent cellular phagocytosis-related genes on the prognosis of metastatic melanoma.PloS one · 2025Article
- Innate immune cell barrier-related genes inform precision prognosis in pancreatic cancer.Frontiers in immunology · 2025Article
- Deciphering the deterministic role of TCR signaling in T cell fate determination.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
T cell responses are inhibited by acidic environments. T cell receptor (TCR)-induced protein phosphorylation is negatively regulated by dephosphorylation and/or ubiquitination, but the mechanisms underlying sensitivity to acidic environments are not fully understood. Here, we found that TCR stimulation induced a molecular complex of Cbl-b, an E3-ubiquitin ligase, with STS1, a pH-sensitive unconventional phosphatase. The induced interaction depended upon a proline motif in Cbl-b interacting with the STS1 SH3 domain. STS1 dephosphorylated Cbl-b interacting phosphoproteins. The deficiency of STS1 or Cbl-b diminished the sensitivity of T cell responses to the inhibitory effects of acid in an autocrine or paracrine manner in vitro or in vivo. Moreover, the deficiency of STS1 or Cbl-b promoted T cell proliferative and differentiation activities in vivo and inhibited tumor growth, prolonged survival, and improved T cell fitness in tumor models. Thus, a TCR-induced STS1-Cbl-b complex senses intra- or extra-cellular acidity and regulates T cell responses, presenting a potential therapeutic target for improving anti-tumor immunity.
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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 Socratic graph.