ArticleJournal of hematology & oncology2020
Antibody targeting tumor-derived soluble NKG2D ligand sMIC reprograms NK cell homeostatic survival and function and enhances melanoma response to PDL1 blockade therapy.
Article in Journal of hematology & oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 40 citations in OpenAlex.
- Inhibition of KDEL Receptors Remodels the Tumor Microenvironment for T Cell Independent Tumor Regression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting the NKG2D axis in head and neck squamous cell carcinoma: from molecular insights to clinical applications.Cancer cell international · 2026Review
- Enhanced CD56 Expression and Increased Number of CD56American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- Targeting NKG2D/NKG2DL axis in cancer immunotherapy: mechanisms and therapeutic applications.Journal of translational medicine · 2026Review
- Immune mechanisms in the pathogenesis of endometriosis: a comprehensive analysis of the role of NK cells, cytokines, and extracellular vesicles/exosomes.Frontiers in immunology · 2026Review
- Chemotherapy driven alterations in NK cell receptors and ligands in high grade serous ovarian cancer.Frontiers in immunology · 2026Article
- Unleashing NK cells for cancer immunotherapy in lung cancer: biologic challenges and clinical advances.Journal of experimental & clinical cancer research : CR · 2025Review
- Article
- ULBP2 Promotes Tumor Progression by Suppressing NKG2D-Mediated Anti-Tumor Immunity.International journal of molecular sciences · 2025Article
- Identification of Natural Killer Cell-Associated Clusters in Skin Melanoma and the Impact on Prognosis and Drug Sensitivity.Immunity, inflammation and disease · 2025Article
- Single-cell transcriptomics identifies FOSL1-regulated IGFBP3+ melanoma subtype as a neuro-immunoregulatory signaling hub facilitating tumor progression.Frontiers in immunology · 2025Article
- Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches.Immunity, inflammation and disease · 2024Review
- A potential mechanism of tumor immune escape: Regulation and application of soluble natural killer group 2 member D ligands (Review).Oncology reports · 2024Review
- Soluble immune checkpoint molecules in cancer risk, outcomes prediction, and therapeutic applications.Biomarker research · 2024Review
- Natural killer cells in cancer immunotherapy.MedComm · 2024Review
- Article
- The Human Soluble NKG2D Ligand Differentially Impacts Tumorigenicity and Progression in Temporal and Model-Dependent Modes.Biomedicines · 2024Article
- Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma.Journal for immunotherapy of cancer · 2024Article
- Chordoma cancer stem cell subpopulation characterization may guide targeted immunotherapy approaches to reduce disease recurrence.Frontiers in oncology · 2024Article
- Soluble NKG2D ligands impair CD8Oncology letters · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMelanoma patients who have detectable serum soluble NKG2D ligands either at the baseline or post-treatment of PD1/PDL1 blockade exhibit poor overall survival. Among families of soluble human NKG2D ligands, the soluble human MHC I chain-related molecule (sMIC) was found to be elevated in melanoma patients and mostly associated with poor response to PD1/PDL1 blockade therapy.
methodsIn this study, we aim to investigate whether co-targeting tumor-released sMIC enhances the therapeutic outcome of PD1/PDL1 blockade therapy for melanoma. We implanted sMIC-expressing B16F10 melanoma tumors into syngeneic host and evaluated therapeutic efficacy of anti-sMIC antibody and anti-PDL1 antibody combination therapy in comparison with monotherapy. We analyzed associated effector mechanism. We also assessed sMIC/MIC prevalence in metastatic human melanoma tumors.
resultsWe found that the combination therapy of the anti-PDL1 antibody with an antibody targeting sMIC significantly improved animal survival as compared to monotherapies and that the effect of combination therapy depends significantly on NK cells. We show that combination therapy significantly increased IL-2Rα (CD25) on NK cells which sensitizes NK cells to low dose IL-2 for survival. We demonstrate that sMIC negatively reprograms gene expression related to NK cell homeostatic survival and proliferation and that antibody clearing sMIC reverses the effect of sMIC and reprograms NK cell for survival. We further show that sMIC/MIC is abundantly present in metastatic human melanoma tumors.
conclusionsOur findings provide a pre-clinical proof-of-concept and a new mechanistic understanding to underscore the significance of antibody targeting sMIC to improve therapeutic efficacy of anti-PD1/PDL1 antibody for MIC/sMIC
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.