The Wdr5-H3K4me3 Epigenetic Axis Regulates Pancreatic Tumor Immunogenicity and Immune Suppression
Abstract
:1. Introduction
2. Results
2.1. WDR5 Expression Profiles in Human Cancer
2.2. WDR5 Expression Positively Correlates with HLA Expression in Human Cancer
2.3. Wdr5 Regulates MHC I Expression in Pancreatic Tumor Cells In Vitro
2.4. Wdr5 Controls MHC I Expression in Pancreatic Tumor Cells In Vivo
2.5. Inhibition of Wdr5 Represses MHC I Expression
2.6. Wdr5-H3K4m3 Axis Regulates MHC I Expression in Mouse Pancreatic Tumor Cells
2.7. WDR5 Deficiency Inhibits Immune Checkpoints and Immune Suppressive Cytokines’ Expression in Pancreatic Tumor Microenvironment
3. Discussion
4. Materials and Methods
4.1. Patient Dataset Analysis
4.2. Human Tumor Specimens
4.3. Mice
4.4. Cell Lines
4.5. Immunohistochemistry
4.6. CRISPR-Based Gene Knockout
4.7. Western Blotting Analysis
4.8. Gene Expression Analysis
4.9. Cell Viability Assay
4.10. Flow Cytometry
4.11. In Vivo Tumor Mouse Model
4.12. CD45+ Cells Isolation
4.13. WDR5-47 Synthesis
4.14. Chromatin Immunoprecipitation (ChIP) Assay
4.15. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Zhang, L.; Lu, Q.; Chang, C. Epigenetics in Health and Disease. Adv. Exp. Med. Biol. 2020, 1253, 3–55. [Google Scholar]
- Hanahan, D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022, 12, 31–46. [Google Scholar] [CrossRef] [PubMed]
- Shvedunova, M.; Akhtar, A. Modulation of cellular processes by histone and non-histone protein acetylation. Nat. Rev. Mol. Cell Biol. 2022, 23, 329–349. [Google Scholar] [CrossRef] [PubMed]
- Black, J.C.; Van Rechem, C.; Whetstine, J.R. Histone lysine methylation dynamics: Establishment, regulation, and biological impact. Mol. Cell 2012, 48, 491–507. [Google Scholar] [CrossRef] [PubMed]
- Flavahan, W.A.; Gaskell, E.; Bernstein, B.E. Epigenetic plasticity and the hallmarks of cancer. Science 2017, 357, eaal2380. [Google Scholar] [CrossRef] [PubMed]
- Kouzarides, T. Chromatin modifications and their function. Cell 2007, 128, 693–705. [Google Scholar] [CrossRef]
- Hughes, A.L.; Kelley, J.R.; Klose, R.J. Understanding the interplay between CpG island-associated gene promoters and H3K4 methylation. Biochim. Biophys. Acta Gene Regul. Mech. 2020, 1863, 194567. [Google Scholar] [CrossRef] [PubMed]
- Sze, C.C.; Cao, K.; Collings, C.K.; Marshall, S.A.; Rendleman, E.J.; Ozark, P.A.; Chen, F.X.; Morgan, M.A.; Wang, L.; Shilatifard, A. Histone H3K4 methylation-dependent and -independent functions of Set1A/COMPASS in embryonic stem cell self-renewal and differentiation. Genes. Dev. 2017, 31, 1732–1737. [Google Scholar] [CrossRef]
- Liu, X.; Wang, C.; Liu, W.; Li, J.; Li, C.; Kou, X.; Chen, J.; Zhao, Y.; Gao, H.; Wang, H.; et al. Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos. Nature 2016, 537, 558–562. [Google Scholar] [CrossRef]
- Yan, M.; Yang, X.; Wang, H.; Shao, Q. The critical role of histone lysine demethylase KDM2B in cancer. Am. J. Transl. Res. 2018, 10, 2222–2233. [Google Scholar]
- Marschalek, R. MLL leukemia and future treatment strategies. Arch. Pharm. 2015, 348, 221–228. [Google Scholar] [CrossRef] [PubMed]
- Cao, F.; Townsend, E.C.; Karatas, H.; Xu, J.; Li, L.; Lee, S.; Liu, L.; Chen, Y.; Ouillette, P.; Zhu, J.; et al. Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia. Mol. Cell 2014, 53, 247–261. [Google Scholar] [CrossRef]
- Wang, P.; Lin, C.; Smith, E.R.; Guo, H.; Sanderson, B.W.; Wu, M.; Gogol, M.; Alexander, T.; Seidel, C.; Wiedemann, L.M.; et al. Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II. Mol. Cell. Biol. 2009, 29, 6074–6085. [Google Scholar] [CrossRef]
- Garcia-Cuellar, M.P.; Büttner, C.; Bartenhagen, C.; Dugas, M.; Slany, R.K. Leukemogenic MLL-ENL Fusions Induce Alternative Chromatin States to Drive a Functionally Dichotomous Group of Target Genes. Cell Rep. 2016, 15, 310–322. [Google Scholar] [CrossRef]
- Li, Y.; Han, J.; Zhang, Y.; Cao, F.; Liu, Z.; Li, S.; Wu, J.; Hu, C.; Wang, Y.; Shuai, J.; et al. Structural basis for activity regulation of MLL family methyltransferases. Nature 2016, 530, 447–452. [Google Scholar] [CrossRef] [PubMed]
- Bolshan, Y.; Getlik, M.; Kuznetsova, E.; Wasney, G.A.; Hajian, T.; Poda, G.; Nguyen, K.T.; Wu, H.; Dombrovski, L.; Dong, A.; et al. Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction. ACS Med. Chem. Lett. 2013, 4, 353–357. [Google Scholar] [CrossRef] [PubMed]
- Li, D.D.; Chen, W.L.; Xu, X.L.; Jiang, F.; Wang, L.; Xie, Y.Y.; Zhang, X.J.; Guo, X.K.; You, Q.D.; Sun, H.P. Structure-based design and synthesis of small molecular inhibitors disturbing the interaction of MLL1-WDR5. Eur. J. Med. Chem. 2016, 118, 1–8. [Google Scholar] [CrossRef]
- Lu, C.; Liu, Z.; Klement, J.D.; Yang, D.; Merting, A.D.; Poschel, D.; Albers, T.; Waller, J.L.; Shi, H.; Liu, K. WDR5-H3K4me3 epigenetic axis regulates OPN expression to compensate PD-L1 function to promote pancreatic cancer immune escape. J. Immunother. Cancer 2021, 9, e002624. [Google Scholar] [CrossRef]
- Lu, C.; Paschall, A.V.; Shi, H.; Savage, N.; Waller, J.L.; Sabbatini, M.E.; Oberlies, N.H.; Pearce, C.; Liu, K. The MLL1-H3K4me3 Axis-Mediated PD-L1 Expression and Pancreatic Cancer Immune Evasion. J. Natl. Cancer Inst. 2017, 109, djw283. [Google Scholar] [CrossRef]
- Xiao, C.; Fan, T.; Zheng, Y.; Tian, H.; Deng, Z.; Liu, J.; Li, C.; He, J. H3K4 trimethylation regulates cancer immunity: A promising therapeutic target in combination with immunotherapy. J. Immunother. Cancer 2023, 11, e005693. [Google Scholar] [CrossRef]
- Guarnaccia, A.D.; Tansey, W.P. Moonlighting with WDR5: A Cellular Multitasker. J. Clin. Med. 2018, 7, 21. [Google Scholar] [CrossRef] [PubMed]
- Rao, M.; Chinnasamy, N.; Hong, J.A.; Zhang, Y.; Zhang, M.; Xi, S.; Liu, F.; Marquez, V.E.; Morgan, R.A.; Schrump, D.S. Inhibition of histone lysine methylation enhances cancer-testis antigen expression in lung cancer cells: Implications for adoptive immunotherapy of cancer. Cancer Res. 2011, 71, 4192–4204. [Google Scholar] [CrossRef] [PubMed]
- Salmaninejad, A.; Zamani, M.R.; Pourvahedi, M.; Golchehre, Z.; Hosseini Bereshneh, A.; Rezaei, N. Cancer/Testis Antigens: Expression, Regulation, Tumor Invasion, and Use in Immunotherapy of Cancers. Immunol. Investig. 2016, 45, 619–640. [Google Scholar] [CrossRef] [PubMed]
- Burr, M.L.; Sparbier, C.E.; Chan, K.L.; Chan, Y.C.; Kersbergen, A.; Lam, E.Y.N.; Azidis-Yates, E.; Vassiliadis, D.; Bell, C.C.; Gilan, O.; et al. An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer. Cancer Cell 2019, 36, 385–401.e8. [Google Scholar] [CrossRef] [PubMed]
- Zhu, J.; Li, L.; Tong, J.; Hui, C.; Wong, C.H.; Lo, K.W.; Chan, R.; Ai, Q.Y.; Hui, E.P.; Chan, A.T.; et al. Targeting the polycomb repressive complex-2 related proteins with novel combinational strategies for nasopharyngeal carcinoma. Am. J. Cancer Res. 2020, 10, 3267–3284. [Google Scholar] [PubMed]
- Cao, W.; Guo, J.; Wen, X.; Miao, L.; Lin, F.; Xu, G.; Ma, R.; Yin, S.; Hui, Z.; Chen, T.; et al. CXXC finger protein 1 is critical for T-cell intrathymic development through regulating H3K4 trimethylation. Nat. Commun. 2016, 7, 11687. [Google Scholar] [CrossRef] [PubMed]
- Harker, N.; Garefalaki, A.; Menzel, U.; Ktistaki, E.; Naito, T.; Georgopoulos, K.; Kioussis, D. Pre-TCR signaling and CD8 gene bivalent chromatin resolution during thymocyte development. J. Immunol. 2011, 186, 6368–6377. [Google Scholar] [CrossRef] [PubMed]
- Wang, W.; Meng, Y.; Chen, Y.; Yu, Y.; Wang, H.; Yang, S.; Sun, W. A comprehensive analysis of LMO2 pathogenic regulatory profile during T-lineage development and leukemic transformation. Oncogene 2022, 41, 4079–4090. [Google Scholar] [CrossRef]
- Akimzhanov, A.; Krenacs, L.; Schlegel, T.; Klein-Hessling, S.; Bagdi, E.; Stelkovics, E.; Kondo, E.; Chuvpilo, S.; Wilke, P.; Avots, A.; et al. Epigenetic changes and suppression of the nuclear factor of activated T cell 1 (NFATC1) promoter in human lymphomas with defects in immunoreceptor signaling. Am. J. Pathol. 2008, 172, 215–224. [Google Scholar] [CrossRef]
- Yuan, X.; Liu, Y.; Li, G.; Lan, Z.; Ma, M.; Li, H.; Kong, J.; Sun, J.; Hou, G.; Hou, X.; et al. Blockade of Immune-Checkpoint B7-H4 and Lysine Demethylase 5B in Esophageal Squamous Cell Carcinoma Confers Protective Immunity against P. gingivalis Infection. Cancer Immunol. Res. 2019, 7, 1440–1456. [Google Scholar] [CrossRef]
- Guenther, C.; Faisal, I.; Fusciello, M.; Sokolova, M.; Harjunpää, H.; Ilander, M.; Tallberg, R.; Vartiainen, M.K.; Alon, R.; Gonzalez-Granado, J.M.; et al. β2-Integrin Adhesion Regulates Dendritic Cell Epigenetic and Transcriptional Landscapes to Restrict Dendritic Cell Maturation and Tumor Rejection. Cancer Immunol. Res. 2021, 9, 1354–1369. [Google Scholar] [CrossRef] [PubMed]
- Sasidharan Nair, V.; El Salhat, H.; Taha, R.Z.; John, A.; Ali, B.R.; Elkord, E. DNA methylation and repressive H3K9 and H3K27 trimethylation in the promoter regions of PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, and PD-L1 genes in human primary breast cancer. Clin. Epigenetics 2018, 10, 78. [Google Scholar] [CrossRef] [PubMed]
- Sasidharan Nair, V.; Saleh, R.; Toor, S.M.; Taha, R.Z.; Ahmed, A.A.; Kurer, M.A.; Murshed, K.; Abu Nada, M.; Elkord, E. Epigenetic regulation of immune checkpoints and T cell exhaustion markers in tumor-infiltrating T cells of colorectal cancer patients. Epigenomics 2020, 12, 1871–1882. [Google Scholar] [CrossRef] [PubMed]
- Logie, C.; Stunnenberg, H.G. Epigenetic memory: A macrophage perspective. Semin. Immunol. 2016, 28, 359–367. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Yang, H.; Zhao, J.; Wan, P.; Hu, Y.; Lv, K.; Hu, Y.; Yang, X.; Ma, M. Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer. J. Immunother. Cancer 2021, 9, e001364. [Google Scholar] [CrossRef] [PubMed]
- Li, L.; Wang, Y.; Mou, Y.; Wu, H.; Qin, Y. KDM1A Identified as a Potential Oncogenic Driver and Prognostic Biomarker via Multi-Omics Analysis. Can. J. Infect. Dis. Med. Microbiol. 2021, 2021, 4668565. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Z.; Huang, X.; Wang, E.; Huang, Y.; Yang, R. Suppression of Mll1-Complex by Stat3/Cebpβ-Induced miR-21a/21b/181b Maintains the Accumulation, Homeostasis, and Immunosuppressive Function of Polymorphonuclear Myeloid-Derived Suppressor Cells. J. Immunol. 2020, 204, 3400–3415. [Google Scholar] [CrossRef] [PubMed]
- Gao, Y.; Wang, T.; Li, Y.; Zhang, Y.; Yang, R. Lnc-chop Promotes Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor and Inflammatory Environments. J. Immunol. 2018, 200, 2603–2614. [Google Scholar] [CrossRef] [PubMed]
- Pelka, K.; Hofree, M.; Chen, J.H.; Sarkizova, S.; Pirl, J.D.; Jorgji, V.; Bejnood, A.; Dionne, D.; Ge, W.H.; Xu, K.H.; et al. Spatially organized multicellular immune hubs in human colorectal cancer. Cell 2021, 184, 4734–4752.e20. [Google Scholar] [CrossRef]
- Wu, S.Z.; Al-Eryani, G.; Roden, D.L.; Junankar, S.; Harvey, K.; Andersson, A.; Thennavan, A.; Wang, C.; Torpy, J.R.; Bartonicek, N.; et al. A single-cell and spatially resolved atlas of human breast cancers. Nat. Genet. 2021, 53, 1334–1347. [Google Scholar] [CrossRef]
- Tian, J.; Chen, J.H.; Chao, S.X.; Pelka, K.; Giannakis, M.; Hess, J.; Burke, K.; Jorgji, V.; Sindurakar, P.; Braverman, J.; et al. Combined PD-1, BRAF and MEK inhibition in BRAF(V600E) colorectal cancer: A phase 2 trial. Nat. Med. 2023, 29, 458–466. [Google Scholar] [CrossRef] [PubMed]
- Sade-Feldman, M.; Yizhak, K.; Bjorgaard, S.L.; Ray, J.P.; de Boer, C.G.; Jenkins, R.W.; Lieb, D.J.; Chen, J.H.; Frederick, D.T.; Barzily-Rokni, M.; et al. Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma. Cell 2018, 175, 998–1013.e20. [Google Scholar] [CrossRef] [PubMed]
- Hazini, A.; Fisher, K.; Seymour, L. Deregulation of HLA-I in cancer and its central importance for immunotherapy. J. Immunother. Cancer 2021, 9, e002899. [Google Scholar] [CrossRef] [PubMed]
- Chi, P.; Allis, C.D.; Wang, G.G. Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers. Nat. Rev. Cancer 2010, 10, 457–469. [Google Scholar] [CrossRef] [PubMed]
- Shilatifard, A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr. Opin. Cell Biol. 2008, 20, 341–348. [Google Scholar] [CrossRef] [PubMed]
- Ruthenburg, A.J.; Allis, C.D.; Wysocka, J. Methylation of lysine 4 on histone H3: Intricacy of writing and reading a single epigenetic mark. Mol. Cell 2007, 25, 15–30. [Google Scholar] [CrossRef]
- Dou, Y.; Milne, T.A.; Tackett, A.J.; Smith, E.R.; Fukuda, A.; Wysocka, J.; Allis, C.D.; Chait, B.T.; Hess, J.L.; Roeder, R.G. Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 2005, 121, 873–885. [Google Scholar] [CrossRef]
- Dou, Y.; Hess, J.L. Mechanisms of transcriptional regulation by MLL and its disruption in acute leukemia. Int. J. Hematol. 2008, 87, 10–18. [Google Scholar] [CrossRef]
- Ayton, P.M.; Cleary, M.L. Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene 2001, 20, 5695–5707. [Google Scholar] [CrossRef]
- Shilatifard, A. The COMPASS family of histone H3K4 methylases: Mechanisms of regulation in development and disease pathogenesis. Annu. Rev. Biochem. 2012, 81, 65–95. [Google Scholar] [CrossRef]
- Dou, Y.; Milne, T.A.; Ruthenburg, A.J.; Lee, S.; Lee, J.W.; Verdine, G.L.; Allis, C.D.; Roeder, R.G. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat. Struct. Mol. Biol. 2006, 13, 713–719. [Google Scholar] [CrossRef] [PubMed]
- Zhang, P.; Lee, H.; Brunzelle, J.S.; Couture, J.F. The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases. Nucleic Acids Res. 2012, 40, 4237–4246. [Google Scholar] [CrossRef] [PubMed]
- Wysocka, J.; Swigut, T.; Milne, T.A.; Dou, Y.; Zhang, X.; Burlingame, A.L.; Roeder, R.G.; Brivanlou, A.H.; Allis, C.D. WDR5 associates with histone H3 methylated at K4 and is essential for H3K4 methylation and vertebrate development. Cell 2005, 121, 859–872. [Google Scholar] [CrossRef]
- Patel, A.; Dharmarajan, V.; Cosgrove, M.S. Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide. J. Biol. Chem. 2008, 283, 32158–32161. [Google Scholar] [CrossRef]
- Senisterra, G.; Wu, H.; Allali-Hassani, A.; Wasney, G.A.; Barsyte-Lovejoy, D.; Dombrovski, L.; Dong, A.; Nguyen, K.T.; Smil, D.; Bolshan, Y.; et al. Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5. Biochem. J. 2013, 449, 151–159. [Google Scholar] [CrossRef]
- Ji, A.; Qian, L.; Tian, Z.; Cui, J. WDR5 promotes the proliferation of lung adenocarcinoma by inducing SOX9 expression. Biomark. Med. 2021, 15, 1599–1609. [Google Scholar] [CrossRef] [PubMed]
- Lyu, X.Y.; Shui, Y.S.; Wang, L.; Jiang, Q.S.; Meng, L.X.; Zhan, H.Y.; Yang, R. WDR5 promotes the tumorigenesis of oral squamous cell carcinoma via CARM1/β-catenin axis. Odontology 2022, 110, 138–147. [Google Scholar] [CrossRef]
- Mitchell, K.; Sprowls, S.A.; Arora, S.; Shakya, S.; Silver, D.J.; Goins, C.M.; Wallace, L.; Roversi, G.; Schafer, R.E.; Kay, K.; et al. WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma. Genes. Dev. 2023, 37, 86–102. [Google Scholar] [CrossRef]
- Chen, X.; Lu, Q.; Zhou, H.; Liu, J.; Nadorp, B.; Lasry, A.; Sun, Z.; Lai, B.; Rona, G.; Zhang, J.; et al. A membrane-associated MHC-I inhibitory axis for cancer immune evasion. Cell 2023, 186, 3903–3920.e21. [Google Scholar] [CrossRef]
- Zhang, B.; Li, J.; Hua, Q.; Wang, H.; Xu, G.; Chen, J.; Zhu, Y.; Li, R.; Liang, Q.; Wang, L.; et al. Tumor CEMIP drives immune evasion of colorectal cancer via MHC-I internalization and degradation. J. Immunother. Cancer 2023, 11, e005592. [Google Scholar] [CrossRef]
- Ren, J.; Li, N.; Pei, S.; Lian, Y.; Li, L.; Peng, Y.; Liu, Q.; Guo, J.; Wang, X.; Han, Y.; et al. Histone methyltransferase WHSC1 loss dampens MHC-I antigen presentation pathway to impair IFN-γ-stimulated antitumor immunity. J. Clin. Investig. 2022, 132, e153167. [Google Scholar] [CrossRef]
- Zhou, Y.; Bastian, I.N.; Long, M.D.; Dow, M.; Li, W.; Liu, T.; Ngu, R.K.; Antonucci, L.; Huang, J.Y.; Phung, Q.T.; et al. Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation. Proc. Natl. Acad. Sci. USA 2021, 118, e2025840118. [Google Scholar] [CrossRef] [PubMed]
- Punzi, S.; Balestrieri, C.; D’Alesio, C.; Bossi, D.; Dellino, G.I.; Gatti, E.; Pruneri, G.; Criscitiello, C.; Lovati, G.; Meliksetyan, M.; et al. WDR5 inhibition halts metastasis dissemination by repressing the mesenchymal phenotype of breast cancer cells. Breast Cancer Res. 2019, 21, 123. [Google Scholar] [CrossRef] [PubMed]
- Xu, W.; Zhao, Q.; Wu, M.; Fang, M.; Xu, Y. MKL1 mediates TNF-α induced pro-inflammatory transcription by bridging the crosstalk between BRG1 and WDR5. J. Biomed. Res. 2019, 33, 164–172. [Google Scholar] [CrossRef] [PubMed]
- Dang, B.; Gao, Q.; Zhang, L.; Zhang, J.; Cai, H.; Zhu, Y.; Zhong, Q.; Liu, J.; Niu, Y.; Mao, K.; et al. The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages. Cell Rep. 2023, 42, 112471. [Google Scholar] [CrossRef]
- Yu, X.; Li, D.; Kottur, J.; Shen, Y.; Kim, H.S.; Park, K.S.; Tsai, Y.H.; Gong, W.; Wang, J.; Suzuki, K.; et al. A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models. Sci. Transl. Med. 2021, 13, eabj1578. [Google Scholar] [CrossRef]
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Deng, K.; Liang, L.; Yang, Y.; Wu, Y.; Li, Y.; Zhang, R.; Tian, Y.; Lu, C. The Wdr5-H3K4me3 Epigenetic Axis Regulates Pancreatic Tumor Immunogenicity and Immune Suppression. Int. J. Mol. Sci. 2024, 25, 8773. https://doi.org/10.3390/ijms25168773
Deng K, Liang L, Yang Y, Wu Y, Li Y, Zhang R, Tian Y, Lu C. The Wdr5-H3K4me3 Epigenetic Axis Regulates Pancreatic Tumor Immunogenicity and Immune Suppression. International Journal of Molecular Sciences. 2024; 25(16):8773. https://doi.org/10.3390/ijms25168773
Chicago/Turabian StyleDeng, Kaidi, Liyan Liang, Yingcui Yang, Yanmin Wu, Yan Li, Rongrong Zhang, Yulin Tian, and Chunwan Lu. 2024. "The Wdr5-H3K4me3 Epigenetic Axis Regulates Pancreatic Tumor Immunogenicity and Immune Suppression" International Journal of Molecular Sciences 25, no. 16: 8773. https://doi.org/10.3390/ijms25168773