ArticleMolecular cancer2024
Mutation status of the KMT2 family associated with immune checkpoint inhibitors (ICIs) therapy and implicating diverse tumor microenvironments.
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Dysregulated KMT2D mutant targeting immunogenic rewiring to overcome epigenetic entropy promotes follicular lymphomagenesis.Experimental hematology & oncology · 2026Article
- Translational perspectives on immunotherapy targets, germline syndromes, and novel fusions.The oncologist · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Loss of Kmt2c/d promotes gastric cancer and confers vulnerability to mTORC1 and PD-1 inhibition.The Journal of clinical investigation · 2026Article
- Distinct genomic landscape of colorectal signet ring cell carcinoma reveals frequent KMT2 family alterations and SMAD4 inactivation.BMC cancer · 2026Article
- Histone Methylation and Chromatin Remodeling in Non-Small Cell Lung Cancer: Mechanisms of Oncogenesis and Emerging Therapeutic Strategies.Biomedicines · 2026Review
- Review
- Next generation sequencing identifies novel gene alterations with potential prognostic relevance in pediatric cancer: a single-center study.The oncologist · 2026Article
- Elevated T Cell Immunoreceptor with Ig and ITIM Domains (TIGIT) Expression and Immune Cell Dysfunction Characterize Complex Proteins Associated With SET1 (COMPASS)-Like Complex Gene-Mutated Pancreatic Ductal Adenocarcinoma (PDAC).Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026Article
- Review
- First-line immunotherapy for advanced HER2-negative gastric cancer: differences between Asian and non-Asian patients.Cancer biology & medicine · 2026Review
- OncoBERT: Context-Aware Modeling of Somatic Mutations for Precision Oncology.bioRxiv : the preprint server for biology · 2026Article
- Identification of a chromatin-modifying gene-histone lysine N-methyl transferase (KMT2C/MLL3) as a potential immunomodulator oncogene in Indian pancreatic cancer patients.European journal of medical research · 2025Article
- Silencing KMT2A with siRNA induces apoptosis and cell cycle arrest in high-grade serous ovarian carcinoma cells by modulating GOF p53-dependent pathways, highlighting its potential as a therapeutic target.Medical oncology (Northwood, London, England) · 2025Article
- TPD52 promotes the proliferation and metastasis of gastric cancer cells.BMC gastroenterology · 2025Article
- [Clinical characteristics and prognosis of 18 patients with plasmablastic lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- KMT2D/ZNF460-induced COL9A1-mediated extracellular matrix stiffness maintains the cancer stem cell pool to promote colorectal cancer progression.Cell biology and toxicology · 2025Article
- Whole genome sequencing and single-cell transcriptomics identify KMT2D inactivation as a potential new driver for pituitary tumors: a case report.BJC reports · 2025Article
- The FBXW7-KMT2 axis in cancer-associated fibroblasts controls tumor growth via an epigenetic-paracrine mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lysine methyltransferase 2D deficiency drives complete response to pembrolizumab in PD-L1-High cholangiocarcinoma: a case report and review of literature.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts (n = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival (P < 0.001, hazard ratio [HR] = 0.733 [95% confidence interval (CI): 0.632-0.850]), progression-free survival (P = 0.002, HR = 0.669 [95% CI: 0.518-0.864]), durable clinical benefit (P < 0.001, 54.1% vs. 32.6%), and objective response rate (P < 0.001, 40.6% vs. 22.0%). Through a comprehensive analysis of the tumor microenvironment across different KMT2 mutation statuses, we observed that tumors harboring the KMT2 mutation exhibited enhanced immunogenicity, increased infiltration of immune cells, and higher levels of immune cell cytotoxicity, suggesting a propensity towards a "hot tumor" phenotype. Therefore, our study indicates a potential association between KMT2 mutations and a more favorable response to ICI therapy and implicates different tumor microenvironments associated with ICI therapy response.
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