ArticleJournal of molecular medicine (Berlin, Germany)2020
The integrated stress response promotes B7H6 expression.
Article in Journal of molecular medicine (Berlin, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 50 citations in OpenAlex.
- The Unfolded Protein Response as a Modulator of Cancer-Immune Cell Communication in the Tumour Microenvironment.Journal of cellular and molecular medicine · 2026Review
- B7-H6/NKp30 Axis in Melanoma: Translational Rationale, Evidence Gaps, and Therapeutic Considerations.Biomolecules · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- CRISPR/Cas9 TCR-Edited NKp30 CAR T Cells Exhibit Superior Anti-Tumor Immunity to B7H6-Expressing Leukemia and Melanoma.International journal of molecular sciences · 2025Article
- Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025Review
- Unravelling the antitumor mechanism of Ocoxin through cancer cell genomics.Frontiers in pharmacology · 2025Article
- Harnessing B7-H6 for Anticancer Immunotherapy: Expression, Pathways, and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Endoplasmic reticulum stress in diseases.MedComm · 2024Review
- Article
- The Role of Natural Killer Cells in the Tumor Immune Microenvironment of EBV-Associated Nasopharyngeal Carcinoma.Cancers · 2024Review
- Nelfinavir inhibition of Kaposi's sarcoma-associated herpesvirus protein expression and capsid assembly.Infectious agents and cancer · 2024Article
- Tumorous IRE1α facilitates CD8Cell communication and signaling : CCS · 2024Article
- Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression.Frontiers in immunology · 2024Article
- Nelfinavir Inhibition of Kaposi's sarcoma-associated herpesvirus protein expression and capsid assembly.Research square · 2023Article
- Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands.Therapeutic advances in vaccines and immunotherapy · 2023Review
- Decoding endoplasmic reticulum stress signals in cancer cells and antitumor immunity.Trends in cancer · 2022Review
- Bromodomain protein BRD4 is an epigenetic activator of B7-H6 expression in acute myeloid leukemia.Oncoimmunology · 2021Article
- Endoplasmic reticulum stress signals in the tumour and its microenvironment.Nature reviews. Cancer · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The B7 family member, B7H6, is a ligand for the natural killer cell receptor NKp30. B7H6 is hardly expressed on normal tissues, but undergoes upregulation on different types of tumors, implicating it as an attractive target for cancer immunotherapy. The molecular mechanisms that control B7H6 expression are poorly understood. We report that in contrast to other NK cell ligands, endoplasmic reticulum (ER) stress upregulates B7H6 mRNA levels and surface expression. B7H6 induction by ER stress requires protein kinase R-like ER kinase (PERK), one of the three canonical sensors of the unfolded protein response. PERK phosphorylates eIF2α, which regulates protein synthesis and gene expression. Because eIF2α is phosphorylated by several kinases following different stress conditions, the program downstream to eIF2α phosphorylation is called the integrated stress response (ISR). Several drugs were reported to promote the ISR. Nelfinavir and lopinavir, two clinically approved HIV protease inhibitors, promote eIF2α phosphorylation by different mechanisms. We show that nelfinavir and lopinavir sustainably instigate B7H6 expression at their pharmacologically relevant concentrations. As such, ER stress and ISR conditions sensitize melanoma targets to CAR-T cells directed against B7H6. Our study highlights a novel mechanism to induce B7H6 expression and suggests a pharmacological approach to improve B7H6-directed immunotherapy. KEY MESSAGES: B7H6 is induced by ER stress in a PERK-dependent mechanism. Induction of B7H6 is obtained pharmacologically by HIV protease inhibitors. Exposure of tumor cells to the HIV protease inhibitor nelfinavir improves the recognition by B7H6-directed CAR-T.
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.