ArticleCancer research2007
Suppression of proximal T cell receptor signaling and lytic function in CD8+ tumor-infiltrating T cells.
Article in Cancer research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 65 citations in OpenAlex.
- ITPRIPL1: A tumor immune-associated biomarker with prognostic and therapeutic implications in gastrointestinal cancer.Scientific reports · 2026Article
- Discovery of a First-in-Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity.Angewandte Chemie (International ed. in English) · 2026Article
- Consideration of SHP-1 as a Molecular Target for Tumor Therapy.International journal of molecular sciences · 2023Review
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Small molecule inhibitors for cancer immunotherapy and associated biomarkers - the current status.Frontiers in immunology · 2023Review
- Nature vs. Nurture: The Two Opposing Behaviors of Cytotoxic T Lymphocytes in the Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Biomechanics of T Cell Dysfunctions in Chronic Diseases.Frontiers in immunology · 2021Review
- PD-1 suppresses the maintenance of cell couples between cytotoxic T cells and target tumor cells within the tumor.Science signaling · 2020Article
- Radiotherapy Cooperates with IL15 to Induce Antitumor Immune Responses.Cancer immunology research · 2020Article
- Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression.Cell communication and signaling : CCS · 2020Article
- Shp1 in Solid Cancers and Their Therapy.Frontiers in oncology · 2020Review
- Exosomes Associated with Human Ovarian Tumors Harbor a Reversible Checkpoint of T-cell Responses.Cancer immunology research · 2018Article
- Kv1.3 Channels Mark Functionally Competent CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Cancer.Cancer research · 2017Article
- Review
- A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors.Cancer research · 2016Article
- Identification of Candidate Tolerogenic CD8(+) T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model.Journal of diabetes research · 2016Article
- Metabolic communication in tumors: a new layer of immunoregulation for immune evasion.Journal for immunotherapy of cancer · 2016Review
- Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation.The Journal of experimental medicine · 2015Article
- Extracellular Vesicles Present in Human Ovarian Tumor Microenvironments Induce a Phosphatidylserine-Dependent Arrest in the T-cell Signaling Cascade.Cancer immunology research · 2015Article
- Myeloid-derived suppressor cells in B cell malignancies.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
CD8(+) tumor-infiltrating lymphocytes (TIL) lack in vivo and in vitro lytic function due to a signaling deficit characterized by failure to flux calcium or activate tyrosine kinase activity upon contact with cognate tumor cells. Although CD3 zeta is phosphorylated by conjugation in vitro with cognate tumor cells, showing that TIL are triggered, PLC gamma-1, LAT, and ZAP70 are not activated and LFA-1 is not affinity-matured, and because p56(lck) is required for LFA-1 activation, this implies that the signaling blockade is very proximal. Here, we show that TIL signaling defects are transient, being reversed upon purification and brief culture in vitro, implying a fast-acting "switch". Biochemical analysis of purified nonlytic TIL shows that contact with tumor cells causes transient activation of p56(lck) ( approximately 10 s) which is rapidly inactivated. In contrast, tumor-induced activation of p56(lck) in lytic TIL is sustained coincident with downstream TCR signaling and lytic function. Shp-1 is robustly active in nonlytic TIL compared with lytic TIL, colocalizes with p56(lck) in nonlytic TIL, and inhibition of Shp-1 activity in lytic TIL in vitro blocks tumor-induced defective TIL cytolysis. Collectively, our data support the notion that contact of nonlytic TIL with tumor cells, and not with tumor-infiltrating myeloid-derived suppressor cells, causes activation of Shp-1 that rapidly dephosphorylates the p56(lck) activation motif (Y394), thus inhibiting effector phase functions.
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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.