聯絡電話
曾鴻泰
副教授
免疫學
腫瘤免疫學
分子生物學
腫瘤生物學
- 電子郵件信箱
htay11@cgmh.org.tw
研究簡介
腫瘤細胞與免疫細胞在腫瘤微環境中的交互作用容易促成腫瘤發展，主要原因在於腫瘤細胞衍生之訊息易於塑造免疫抑制環境的發展而壓制對抗腫瘤之免疫反應。藉由免疫檢查點抑制劑 (immune checkpoint inhibitor)恢復對抗腫瘤之免疫活性而達到抑制腫瘤生長的效果。儘管如此，對於免疫檢查點抑制劑療法展現療效的比例並不高。plasminogen activator inhibitor 1 (PAI-1)是參與血栓與動脈硬化的重要蛋白，也被發現在許多腫瘤組織中有過度表現。在我們的研究中發現PAI-1可以調控腫瘤細胞表面的PD-L1，抑制PAI-1促使腫瘤細胞表面PD-L1增加而提升對免疫檢查點抑制劑敏感度，進而改善免疫抑制劑療法。
另一方面，相對於免疫檢查點抑制劑，化療仍是臨床常使用的療法。我們也發現腫瘤細胞經由自噬作用分泌出PAI-1改變了微環境的免疫細胞因而對化療產生抗性。我們也持續探討腫瘤衍生物質與免疫細胞活性之連結，期望有助於開發新穎腫瘤免疫治療方式。
學術著作
Recent publications (Pubmed Search)
1: Lee WC, Lu S, Su CH, Tain YL, Wu KLH, Hsu CN, Tzeng HT. Tadalafil Ameliorates
Chronic Ischemia-Associated Bladder Overactivity in Fructose-Fed Rats by
Exerting Pelvic Angiogenesis and Enhancing p-eNOS Expression. Int J Mol Sci.
2025 Feb 6;26(3):1363. doi: 10.3390/ijms26031363. PMID: 39941129; PMCID:
PMC11818424.
2: Tain YL, Hou CY, Tzeng HT, Lin SF, Chang-Chien GP, Lee WC, Wu KLH, Yu HR,
Chan JYH, Hsu CN. Effect of Purified Resveratrol Butyrate Ester Monomers against
Hypertension after Maternal High-Fructose Intake in Adult Offspring. Nutrients.
2024 Sep 17;16(18):3132. doi: 10.3390/nu16183132. PMID: 39339732; PMCID:
PMC11435219.
3: Hu JC, Tzeng HT, Lee WC, Li JR, Chuang YC. Promising Experimental Treatment
in Animal Models and Human Studies of Interstitial Cystitis/Bladder Pain
Syndrome. Int J Mol Sci. 2024 Jul 23;25(15):8015. doi: 10.3390/ijms25158015.
PMID: 39125584; PMCID: PMC11312208.
4: Tzeng HT, Lee WC. Impact of Transgenerational Nutrition on Nonalcoholic Fatty
Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and
Immunity. Nutrients. 2024 May 3;16(9):1388. doi: 10.3390/nu16091388. PMID:
38732634; PMCID: PMC11085251.
5: Yu HR, Yeh YT, Tzeng HT, Dai HY, Lee WC, Wu KLH, Chan JYH, Tain YL, Hsu CN.
Carbohydrate-Mediated Pregnancy Gut Microbiota and Neonatal Low Birth Weight.
Nutrients. 2024 Apr 28;16(9):1326. doi: 10.3390/nu16091326. PMID: 38732572;
PMCID: PMC11085476.
6: Tain YL, Hou CY, Chang-Chien GP, Lin S, Tzeng HT, Lee WC, Wu KLH, Yu HR, Chan
JYH, Hsu CN. Reprogramming Effects of Postbiotic Butyrate and Propionate on
Maternal High-Fructose Diet-Induced Offspring Hypertension. Nutrients. 2023 Mar
30;15(7):1682. doi: 10.3390/nu15071682. PMID: 37049522; PMCID: PMC10096847.
7: Tzeng HT, Huang YJ. Tumor Vasculature as an Emerging Pharmacological Target
to Promote Anti-Tumor Immunity. Int J Mol Sci. 2023 Feb 23;24(5):4422. doi:
10.3390/ijms24054422. PMID: 36901858; PMCID: PMC10002465.
8: Huang WT, Weng SW, Tzeng HT, Yen FC, Chiang YS, You HL. Lymphocyte
Subpopulations Associated with Neutralizing Antibody Levels of SARS-CoV-2 for
COVID-19 Vaccination. Vaccines (Basel). 2022 Sep 17;10(9):1550. doi:
10.3390/vaccines10091550. PMID: 36146627; PMCID: PMC9501134.
9: Peng JM, Chen WY, Cheng JH, Luo JW, Tzeng HT. Dysregulation of Cytoskeleton
Remodeling Drives Invasive Leading Cells Detachment. Cancers (Basel). 2021 Nov
11;13(22):5648. doi: 10.3390/cancers13225648. PMID: 34830801; PMCID: PMC8616115.
10: Li LC, Chen WY, Chen JB, Lee WC, Chang CC, Tzeng HT, Huang CC, Chang YJ,
Yang JL. The AST-120 Recovers Uremic Toxin-Induced Cognitive Deficit via NLRP3
Inflammasome Pathway in Astrocytes and Microglia. Biomedicines. 2021 Sep
17;9(9):1252. doi: 10.3390/biomedicines9091252. PMID: 34572437; PMCID:
PMC8467651.
11: Tzeng HT, Chyuan IT, Lai JH. Targeting the JAK-STAT pathway in autoimmune
diseases and cancers: A focus on molecular mechanisms and therapeutic potential.
Biochem Pharmacol. 2021 Nov;193:114760. doi: 10.1016/j.bcp.2021.114760. Epub
2021 Sep 4. PMID: 34492272.
12: Kuo IY, Yang YE, Yang PS, Tsai YJ, Tzeng HT, Cheng HC, Kuo WT, Su WC, Chang
CP, Wang YC. Converged Rab37/IL-6 trafficking and STAT3/PD-1 transcription axes
elicit an immunosuppressive lung tumor microenvironment. Theranostics. 2021 May
12;11(14):7029-7044. doi: 10.7150/thno.60040. PMID: 34093869; PMCID: PMC8171097.
13: Tseng YJ, Lee CH, Chen WY, Yang JL, Tzeng HT. Inhibition of PAI-1 Blocks
PD-L1 Endocytosis and Improves the Response of Melanoma Cells to Immune
Checkpoint Blockade. J Invest Dermatol. 2021 Nov;141(11):2690-2698.e6. doi:
10.1016/j.jid.2021.03.030. Epub 2021 May 14. PMID: 34000287.
14: Tzeng HT, Chyuan IT. Immunometabolism in systemic lupus erythematosus:
Relevant pathogenetic mechanisms and potential clinical applications. J Formos
Med Assoc. 2021 Sep;120(9):1667-1675. doi: 10.1016/j.jfma.2021.03.019. Epub 2021
Apr 6. PMID: 33836940.
15: Tzeng HT, Yang JL, Tseng YJ, Lee CH, Chen WJ, Chyuan IT. Plasminogen
Activator Inhibitor-1 Secretion by Autophagy Contributes to Melanoma Resistance
to Chemotherapy through Tumor Microenvironment Modulation. Cancers (Basel). 2021
Mar 12;13(6):1253. doi: 10.3390/cancers13061253. PMID: 33809137; PMCID:
PMC7999393.
16: Chen WY, Li LC, Wu YH, Yang JL, Tzeng HT. Emerging Roles of
Interleukin-33-responsive Kidney Group 2 Innate Lymphoid Cells in Acute Kidney
Injury. Int J Mol Sci. 2020 Feb 24;21(4):1544. doi: 10.3390/ijms21041544. PMID:
32102434; PMCID: PMC7073188.
17: Tzeng HT, Chyuan IT, Chen WY. Shaping of Innate Immune Response by Fatty
Acid Metabolite Palmitate. Cells. 2019 Dec 13;8(12):1633. doi:
10.3390/cells8121633. PMID: 31847240; PMCID: PMC6952933.
18: Chyuan IT, Tzeng HT, Chen JY. Signaling Pathways of Type I and Type III
Interferons and Targeted Therapies in Systemic Lupus Erythematosus. Cells. 2019
Aug 23;8(9):963. doi: 10.3390/cells8090963. PMID: 31450787; PMCID: PMC6769759.
19: Wang YS, Tzeng HT, Tsai CH, Cheng HC, Lai WW, Liu HS, Wang YC. VAMP8, a
vesicle-SNARE required for RAB37-mediated exocytosis, possesses a tumor
metastasis suppressor function. Cancer Lett. 2018 Nov 28;437:79-88. doi:
10.1016/j.canlet.2018.08.023. Epub 2018 Aug 27. PMID: 30165196.
20: Cho SH, Kuo IY, Lu PF, Tzeng HT, Lai WW, Su WC, Wang YC. Rab37 mediates
exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and
thus suppress lung cancer stemness. Cell Death Dis. 2018 Aug 29;9(9):868. doi:
10.1038/s41419-018-0915-0. PMID: 30158579; PMCID: PMC6115395.
21: Tzeng HT, Su CC, Chang CP, Lai WW, Su WC, Wang YC. Rab37 in lung cancer
mediates exocytosis of soluble ST2 and thus skews macrophages toward tumor-
suppressing phenotype. Int J Cancer. 2018 Oct 1;143(7):1753-1763. doi:
10.1002/ijc.31569. Epub 2018 Jul 3. PMID: 29717487.
22: Tzeng HT, Li TH, Tang YA, Tsai CH, Frank Lu PJ, Lai WW, Chiang CW, Wang YC.
Phosphorylation of Rab37 by protein kinase C alpha inhibits the exocytosis
function and metastasis suppression activity of Rab37. Oncotarget. 2017 Sep
18;8(65):108556-108570. doi: 10.18632/oncotarget.20998. PMID: 29312551; PMCID:
PMC5752464.
23: Tzeng HT, Tsai CH, Yen YT, Cheng HC, Chen YC, Pu SW, Wang YS, Shan YS, Tseng
YL, Su WC, Lai WW, Wu LW, Wang YC. Dysregulation of Rab37-Mediated Cross-talk
between Cancer Cells and Endothelial Cells via Thrombospondin-1 Promotes Tumor
Neovasculature and Metastasis. Clin Cancer Res. 2017 May 1;23(9):2335-2345. doi:
10.1158/1078-0432.CCR-16-1520. Epub 2016 Nov 15. PMID: 28151721.
24: Tzeng HT, Wang YC. Rab-mediated vesicle trafficking in cancer. J Biomed Sci.
2016 Oct 6;23(1):70. doi: 10.1186/s12929-016-0287-7. PMID: 27716280; PMCID:
PMC5053131.
研究團隊
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陳韋如研究助理
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黃瑱芳研究助理
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洪春姿
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黃宜婷工讀生
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學術履歷
EDUCATION:
2007 – 2014 Ph.D.
Graduate Institute of Immunology, College of Medicine,
National Taiwan University, Taipei, Taiwan
PROFESSIONAL EXPERIENCE:
2018/8 ~ present Assistant Professor
Institute for Translational Research in Biomedicine,
Kaohsiung Chang Gung Memorial Hospital,
Kaohsiung, Taiwan
2014/8 ~ 2018/7 Postdoctoral Research Fellow
Department of Pharmacology, College of Medicine,
National Cheng Kung University, Tainan, Taiwan
AWARDS AND RESEARCH SUPPORT:
2017 The third Prize (oral presentation in English), Autumn Camp 2017, The Taiwan Society for
Biochemistry and Molecular Biology
2017 The Second Prize (Thematic oral presentation), 32th Joint Annual Conference of Biomedical
Science (JACBS)
2016 The First Prize (oral presentation), 31th Annual Meeting of Toxicology Society of Taiwan
2016 Travel Grant, International Academic Conference, Ministry of Science and Technology
2012 Travel Grant, Oversea International Academic Conference, Ministry of Education
2012 Travel Grant, aim for the top University Project to the National Taiwan University
2012 Excellent paper Award (oral presentation), The Chinese Society of Immunology
2011 Excellent paper Award (oral presentation), The Chinese Society of Immunology
2010 Excellent paper Award (oral presentation), The Chinese Society of Immunology
RESEARCH INTERESTS:
1. Viral immunology of infectious disease
2. Regulation of T cell activation in cancer
3. Development of immunotherapy for cancer treatment