ArticleCancer research2016
Adaptive NK Cells with Low TIGIT Expression Are Inherently Resistant to Myeloid-Derived Suppressor Cells.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
122 citing papers in PubMed, 2 syntheses or guidelines pooled it, 198 citations in OpenAlex.
- The prognostic effects of circulating myeloid-derived suppressor cells in non-small cell lung cancer: systematic review and meta-analysis.Clinical and experimental medicine · 2023Pooled it
- The prognostic value of myeloid derived suppressor cell level in hepatocellular carcinoma: A systematic review and meta-analysis.PloS one · 2019Pooled it
- Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells.Cancer immunology, immunotherapy : CII · 2018Trial
- Mechanisms of tumor cell evasion from NK cell-mediated killing and advances in NK cell-based cancer immunotherapy.Pharmaceutical science advances · 2026Review
- Ascites reprograms innate lymphoid immune cells in ovarian cancer by promoting ILC2 enrichment and dysfunctional NK-cell states.Journal for immunotherapy of cancer · 2026Article
- Tumor microenvironment-driven natural killer cell diversity: mechanisms and therapeutic opportunities.Cancer biology & medicine · 2026Review
- Expanded adaptive NKG2C+ NK cells exhibit potent ADCC and functional responses against HBV-infected hepatoma cell lines.Cytotherapy · 2026Article
- Functional, Pharmacogenomic, and Immune Landscapes of Long Non-Coding RNAs in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of coinhibitory receptor-expressing non-T cells in inflammation and immunity: unsung heroes or peripheral players?Experimental & molecular medicine · 2025Review
- TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.Cell death & disease · 2025Review
- Oncolytic adeno-immunotherapy improves allogeneic adoptive HER2.CAR-NK function against pancreatic ductal adenocarcinoma.Molecular therapy. Oncology · 2025Article
- Platelets in cancer and immunotherapy: functional dynamics and therapeutic opportunities.Experimental hematology & oncology · 2025Review
- Emerging combined CAR-NK cell therapies in cancer treatment: Finding a dancing partner.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Precision enhancement of CAR-NK cells through non-viral engineering and highly multiplexed base editing.Journal for immunotherapy of cancer · 2025Article
- Trabectedin Enhances the Antitumor Effects of IL-12 in Triple-Negative Breast Cancer.Cancer immunology research · 2025Article
- A PSMA-Targeted Tri-Specific Killer Engager Enhances NK Cell Cytotoxicity against Prostate Cancer.Cancer immunology research · 2025Article
- Myeloid Cells in the Immunosuppressive Microenvironment as Immunotargets in Osteosarcoma.ImmunoTargets and therapy · 2025Review
- Review
- Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization.Signal transduction and targeted therapy · 2024Review
- Review
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Human cytomegalovirus (CMV)-induced adaptive natural killer (NK) cells display distinct phenotypic and functional characteristics, including properties of immune memory. We hypothesized that these cells may be more resistant to suppression mediated by immunoregulatory cell subsets, making them attractive for use in cancer therapy. Here we report that relative to conventional NK cells, adaptive NK cells express lower levels of the inhibitory receptor T-cell Ig and ITIM domain (TIGIT), which results in resistance to immune suppression mediated by myeloid-derived suppressor cells (MDSC), as derived from cytokine induction in normal blood or patients with myelodysplastic syndrome. In contrast, conventional NK cells were potently suppressed by MDSCs, an effect abrogated completely by TIGIT blockade. Mechanistically, TIGIT signaling in NK cells after MDSC coculture led to a decrease in the phosphorylation of ZAP70/Syk and ERK1/2. These effects were reversed by blocking TIGIT on NK cells or by inhibiting production of reactive oxygen species (ROS) by MDSCs, the latter of which upregulated the TIGIT ligand CD155 on MDSCs. Accordingly, the blunted cytotoxicity of NK cells cocultured with MDSCs against tumor cells could be reversed by blocking TIGIT or ROS production. Overall, our results show how adaptive NK cells arising in response to CMV infection can escape MDSC-mediated suppression, and defined TIGIT antagonists as a novel type of checkpoint inhibitor to enhance NK-cell-mediated responses against cancer and infection. Cancer Res; 76(19); 5696-706. ©2016 AACR.
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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.