腫瘤免疫微環境之調控

1. 抗腫瘤免疫反應及腫瘤微環境

近年來關於癌症形成的要素，增加了兩大特點，代謝及免疫逃避。這指出了在癌症的生成及調控，免疫系統扮演著重要角色。癌症的腫瘤微環境是極度複雜的，腫瘤微環境由許多因子組成，包括癌細胞、免疫細胞及基質組織等。腫瘤的發展過程中癌細胞會創造出免疫抑制的微環境，進而逃避免疫系統的抗腫瘤免疫反應。我們先前的研究發現泛素化酶 (E3 ligase) Peli1 可以調控 T 細胞的代謝途徑，進而影響 T 細胞的抗腫瘤免疫反應 。同時，更進一步地發現 E3 ligase 可以調控巨噬細胞上的發炎小體活化 。這些研究說明了 E3 ligase 對於免疫細胞之重要性，並參與抗腫瘤免疫反應之調控。未來，我們將持續深入的探討 Peli1 對於免疫系統之調控，並發展針對 E3 ligase 之治療策略。同時，我們也會針對具有潛力之新基因，研究其在抗腫瘤免疫反應中所扮演之角色。除此之外，近來我們更發現了一個功能尚未完全被鑑定的 E3 ligase，不僅在代謝功能上十分重要，並且在腫瘤微環境當中對於癌細胞或是免疫細胞，均扮演著舉足輕重的角色，影響其恆定，我們將對其所扮演的角色進行深入之探討，釐清其功能並進行機制之探討。

2. 免疫細胞分化、活化及功能之調控

T 細胞在免疫系統當中，扮演著關鍵的角色，可以清除外來病原或是癌細胞。在癌症或是自體免疫疾病中，常常可以發現 T 細胞有不正常的反應出現，因此對於 T 細胞之調控有更深的了解，便有助於發展治療策略。我們利用高通量分析的方式分析了 T 細胞活化之基因圖譜變化，未來我們將針對這些具有潛力的且功能尚未清楚的基因，研究其在 T 細胞活化、功能及分化所扮演的角色。

3. 標靶用藥對於免疫系統之影響

老藥新用一向是個熱門的研究領域，免疫治療結合藥物的共同療法也是目前科學界中相當重要的課題。除此之外，抗藥性與免疫系統間的相關性，所知仍然十分有限。未來我們將針對目前重要的標靶藥物以及具有潛力的藥物，研究其對於免疫反應的影響，並進而研究結合免疫治療對於癌症病人的成效，並發展結合療法的策略，這項研究將大幅提升目前對於標靶藥物的認知，並提供對於未來藥物發展的重要資訊。

1. Han-Yi Chen, Wan-Chen Hsieh, Yu-Chieh Liu, Huei-Ying Li, Po-Yo Liu, Yu-Ting Hsu, Shao-Chun Hsu, An-Chi Luo, Wei-Chen Kuo, Yi-Jhen Huang, Gan-Guang Liou, Meng-Yun Lin, Chun-Jung Ko, Hsing-Chen Tsai & Shu-Jung Chang. Mitochondrial injury induced by a Salmonella genotoxin triggers the proinflammatory senescence-associated secretory phenotype. Nature Communications volume15, Article number: 2778 (2024) 
2. Li Y, Zhu L, Ko CJ, Yang JY, Wang H, Manyam G, Wang J, Cheng X, Zhao S, Jie Z. TRAF3-EWSR1 signaling axis acts as a checkpoint on germinal center responses. J Exp Med (2023) 220 (8): e20221483
3. Lele Zhu, Xiaofei Zhou, Meidi Gu, Jiseong Kim, Yanchuan Li, Chun-Jung Ko, Xiaoping Xie, Tianxiao Gao, Xuhong Cheng, Shao-Cong Sun. Dapl1 controls NFATc2 activation to regulate CD8+ T cell exhaustion and responses in chronic infection and cancer. Nat Cell Biol 2022, 24(7):1165-1176.
4. Hsin-Ying Lin, Chun-Jung Ko, Tzu-Yu Lo, Shang-Ru Wu, Shao-Wei Lan, Chen-An Huang, Yi-Chin Lin, Hsin-Hsien Lin, Hsin-Fang Tu, Cheng-Fan Lee, Pei-Wen Hsiao, Hsiang-Po Huang, Mei-Jou Chen, Kai-Hsiung Chang, Ming-Shyue Lee. Matriptase-2/NR4A3 axis switches TGF-β action toward suppression of prostate cancer cell invasion, tumor growth, and metastasis. Oncogene 2022, 41(20): 2833-2845.
5. Tianxiao Gao, Ting Liu, Chun-Jung Ko*, Lingyun Zhang, Donghyun Joo, Xiaoping Xie, Lele Zhu, Yanchuan Li, Xuhong Cheng and Shao-Cong Sun*. Myeloid cell TBK1 restricts inflammatory responses. Proc Natl Acad Sci U S A. 2022: 119, e2107742119, Jan 25 (co-corresponding author and co-first author)
6. Yanchuan Li, Xiaoping Xie, Zuliang Jie, Lele Zhu, Jin-Young Yang, Chun-Jung Ko, Tianxiao Gao, Antrix Jain, Sung Yun Jung, Natalia Baran, Marina Y Konopleva, Xuhong Cheng, Shao-Cong Sun (2021, Dec). DYRK1a mediates BAFF-induced noncanonical NF-κB activation to promote autoimmunity and Bcell leukemogenesis. Blood, 138(23):2360-2371.
7. Lingyun Zhang, Chun-Jung Ko, Yanchuan Li, Zuliang Jie, Lele Zhu, Xiaofei Zhou, Xiaoping Xie, Tianxiao Gao, Ting Liu, Xuhong Cheng, Shao-Cong Sun (2021, Oct). Peli1 facilitates NLRP3 inflammasome activation by mediating ASC ubiquitination. Cell Reports, 37(4):109904. (co-first author)
8. Xie X, Zhu L, Jie Z, Li Y, Gu M, Zhou X, Wang H, Chang JH, Ko CJ, Cheng X, Sun SC (2021, Sep). TRAF2 regulates T cell immunity by maintaining a Tpl2- ERK survival signaling axis in effector and memory CD8 T cells. Cell Mol Immunol, 18(9):2262-2274.
9. Zuliang Jie, Chun-Jung Ko, Hui Wang, Xiaoping Xie, Yanchuan Li, Meidi Gu, Lele Zhu, Jin-Young Yang, Tianxiao Gao, Wenjuan Ru, Shao-Jun Tang, Xuhong Cheng, Shao-Cong Sun (2021, Sep). Microglia promote autoimmune inflammation via the noncanonical NF-κB pathway. SCIENCE ADVANCES, 7(36):eabh0609. (co-first author)
10. Hsin-Fang Tu, Chun-Jung Ko, Ching-Tai Lee, Cheng-Fan Lee, Shao-Wei Lan, Hsin-Hsien Lin, Hsin-Ying Lin, Chia-Chi Ku, Der-Yen Lee, I-Chun Chen, Ya- Hui Chuang, Francisco Del Caño-Ochoa, Santiago Ramón-Maiques, Chao-Chi Ho, Ming-Shyue Lee, Geen-Dong Chang (2021, Jun). Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD. Cancer Research, 81(12):3270-3282.
11. Ko CJ, Zhang L, Jie Z, Zhu L, Zhou X, Xie X, Gao T, Yang JY, Cheng X, Sun SC (2021, Jan). The E3 ubiquitin ligase Peli1 regulates the metabolic actions of mTORC1 to suppress antitumor T cell responses. EMBO Journal, 40(2):e104532.
12. Yang JY, Jie Z, Mathews A, Zhou X, Li Y, Gu M, Xie X, Ko CJ, Cheng X, Qi Y, Estrella JS, Wang J, Sun SC (2020, Nov). Intestinal Epithelial TBK1 Prevents Differentiation of T-helper 17 Cells and Tumorigenesis in Mice. Gastroenterology, 159(5):1793-1806.
13. Ko CJ, Hsu TW, Wu SR, Lan SW, Hsiao TF, Lin HY, Lin HH, Tu HF, Lee CF, Huang CC, Chen MM, Hsiao PW, Huang HP, Lee MS (2020, Sep). Inhibition of TMPRSS2 by HAI-2 reduces prostate cancer cell invasion and metastasis. Oncogene, 39(37):5950-5963. (co-first author)
14. Zhu L, Li Y, Xie X, Zhou X, Gu M, Jie Z, Ko CJ, Gao T, Hernandez BE, Cheng X, Sun SC (2019, Dec). TBKBP1 and TBK1 form a growth factor signalling axis mediating immunosuppression and tumourigenesis. Nat Cell Biol, 21(12):1604- 1614.
15. Lee CF, Dang A, Hernandez E, Pong RC, Chen B, Sonavane R, Raj G, Kapur P, Lin HY, Wu SR, Ko CJ, Lo UG, Lee HY, Hsieh JT, Lee MS (2019, Jul). Activation of sphingosine kinase by lipopolysaccharide promotes prostate cancer cell invasion and metastasis via SphK1/S1PR4/matriptase. Oncogene, 38(28):5580-5598.
16. Wu SR, Lin CH, Shih HP, Ko CJ, Lin HY, Lan SW, Lin HH, Tu HF, Ho CC, Huang HP, Lee MS (2019, Mar). HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis. . Br J Cancer, 120(5):499-511.
17. Wu SR, Teng CH, Tu YT, Ko CJ, Cheng TS, Lan SW, Lin HY, Lin HH, Tu HF, Hsiao PW, Huang HP, Chen CH, Lee MS (2017, Nov). The Kunitz Domain I of Hepatocyte Growth Factor Activator Inhibitor-2 Inhibits Matriptase Activity and Invasive Ability of Human Prostate Cancer Cells. . Sci Rep, 7(1):15101.
18. Ko CJ, Lan SW, Lu YC, Cheng TS, Lai PF, Tsai CH, Hsu TW, Lin HY, Shyu HY, Wu SR, Lin HH, Hsiao PW, Chen CH, Huang HP, Lee MS (2017, Aug). Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis. oncogene, 36(32):4597-4609. (co-first author)

博士班: 林孟筠 椰林優秀博士班獎學金

碩士班: 余思霈 113 沈豐文教授 紀念獎學金 壁報獎

                蔡雨汶 113 沈豐文教授 紀念獎學金 壁報獎, 第39屆 生物醫學聯合學術年會壁報論文優等獎

                連理惠

                莊煒婷

助理:     紀昊辰

大學部: 曾俊迪, 王珮鑫

Alumni:

紀昊辰 (2024 碩士): 第38屆 生物醫學聯合學術年會壁報論文特優獎, 112 沈豐文教授 紀念獎學金 壁報獎 

賴美志 (2024 碩士)

廖絜穎 (2024)

Yumi Sato (2023)

黃品睿 (2023)

王文心 (2022)

Last updated 11/21/2024

2022     2030 Cross-Generation Young Scholars Program, Emerging Young Scholars, The National Science and                   Technology Council (NSTC), Taiwan. (2030跨世代年輕學者計畫新秀學者)

2017     The Postdoctoral Fellow Research Abroad Program, Ministry of Science and Technology,  Taiwan. 

2016     Second place for oral presentation, The 31th Joint Annual Conference of Biomedical  Science, Taiwan.    

2015      Excellent paper award for Ph.D. program, National Taiwan University. 

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