ReviewLaboratory investigation; a journal of technical methods and pathology2009
Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma.
Review in Laboratory investigation; a journal of technical methods and pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 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
168 citing papers in PubMed, 304 citations in OpenAlex.
- Radiotherapy and DNA damage response inhibitors modestly sensitize HNSCC to NK cell killing, with ATM inhibition more effective than ATR inhibition.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Article
- Natural killer cells in ovarian cancer therapy: mechanisms, evasion, and therapeutic innovations.Inflammopharmacology · 2026Review
- BCL-2 inhibition at antiretroviral therapy initiation reduces the intact SIV reservoir in macaques.Nature microbiology · 2026Article
- Granzyme B in age-related macular degeneration: mechanistic insights and therapeutic perspectives.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Article
- Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity.Cancer cell · 2026Article
- Cytotoxic CD4 T Cells: Dual Agents in HIV-1 Pathogenesis and Persistence.Current HIV/AIDS reports · 2026Review
- Unraveling key genes and mitochondrial-related mechanisms of atherosclerosis severity: explorations based on interpretable machine learning.BMC cardiovascular disorders · 2026Article
- Granzyme B from mast cells contributes to choroidal neovascularization in a model of wet age-related macular degeneration.Frontiers in immunology · 2026Article
- Molecular signatures and machine learning driven stress biomarkers for rainbow trout aquaculture and climate adaptation.Scientific reports · 2025Article
- Chemical probes for enzyme imaging: challenges in design, synthesis and biomedical applications.Chemical science · 2025Review
- Bulk RNAseq Analysis of Cardiac Myosin-Specific CD4Biomedicines · 2025Article
- Ex vivo single-cell profiling of acute myocardial infarction patients reveals disproportionate CD66bBioengineering & translational medicine · 2025Article
- Acute kidney injury disrupts cardiac remodeling via SerpinA3N.bioRxiv : the preprint server for biology · 2025Article
- Pathotype-Specific Expression of Granzyme-Perforin Pathway Genes and Their Association With Clinical Disease Activity in Early Rheumatoid Arthritis and in a Randomized Clinical Trial.Immune network · 2025Article
- Effect of IL-1β on NSCLC-Derived Small Extracellular Vesicles as Actors in Mediating Cancer Progression and Evading Immune System.International journal of molecular sciences · 2025Article
- NKG7 is a Stable Marker of Cytotoxicity Across Immune Contexts and Within the Tumor Microenvironment.European journal of immunology · 2025Article
- Rational development of gemcitabine-based nanoplatform for targeting SERPINB9/Granzyme B axis to overcome chemo-immune-resistance.Nature communications · 2025Article
- NLRP4 unlocks an NK/macrophages-centered ecosystem to suppress non-small cell lung cancer.Biomarker research · 2025Article
- Plasma inflammatory and angiogenic protein profiling of patients with sickle cell disease.British journal of haematology · 2025Article
108 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
4 authors at 1 institution in 1 country.
Funding
Abstract
The cytotoxic granzyme B (GrB)/perforin pathway has been traditionally viewed as a primary mechanism that is used by cytotoxic lymphocytes to eliminate allogeneic, virally infected and/or transformed cells. Although originally proposed to have intracellular and extracellular functions, upon the discovery that perforin, in combination with GrB, could induce apoptosis, other potential functions for this protease were, for the most part, disregarded. As there are 5 granzymes in humans and 11 granzymes in mice, many studies used perforin knockout mice as an initial screen to evaluate the role of granzymes in disease. However, in recent years, emerging clinical and biochemical evidence has shown that the latter approach may have overlooked a critical perforin-independent, pathogenic role for these proteases in disease. This review focuses on GrB, the most characterized of the granzyme family, in disease. Long known to be a pro-apoptotic protease expressed by cytotoxic lymphocytes and natural killer cells, it is now accepted that GrB can be expressed in other cell types of immune and nonimmune origin. To the latter, an emerging immune-independent role for GrB has been forwarded due to recent discoveries that GrB may be expressed in nonimmune cells such as smooth muscle cells, keratinocytes, and chondrocytes in certain disease states. Given that GrB retains its activity in the blood, can cleave extracellular matrix, and its levels are often elevated in chronic inflammatory diseases, this protease may be an important contributor to certain pathologies. The implications of sustained elevations of intracellular and extracellular GrB in chronic vascular, dermatological, and neurological diseases, among others, are developing. This review examines, for the first time, the multiple roles of GrB in disease pathogenesis.
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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.