1、The Biology of  MDSCs in cancers.

In the bone marrow, tumor-derived factors block the differentiation of immature myeloid cell to fully mature cells creating an accumulation of pathological activated immature monocytes and neutrophils known as M-MDSCs and PMN-MDSCs, respectively. These two MDSC subsets are able to polarize from a classically activated phenotype (M1) to an alternatively activated one (M2), or vice versa, in tumor-bearing mice. Phenotypic polarization affects MDSC pro-tumoral and anti-tumoral function and cancer progression. However the mechanisms underlying MDSC development from expansion and activation to polarization in cancer remain poorly understood.My group mainly focus on studying the differentiation, accumulation, polarization and function of MDSC in cancers. By screening small molecule drugs of targeting MDSC differentiation, accumulation, polarization and function, my group is exploring the drugs selectively controlling MDSC.

2、Study on the strategy of tumor immunotherapy targeting MDSC lipid metabolism.

Lipid metabolism is an important regulator of MDSC function in tumors  and could contribute to ROS-mediated immune suppression. MDSCs undergo metabolic reprogramming from glycolysis to fatty acid oxidation (FAO) and oxidative phosphorylation led by lipid accumulation in tumor. Increased exogenous fatty acid uptake by tumor MDSCs enhance their immunosuppressive activity on T-cells thus promoting tumor progression.Which genes and signaling pathways regulate lipid metabolism of MDSC remain unclear. By targeting  TIPE2, FATP2、DGAT1 and CD317 lipid metabolism genes of MDSCs, my group is exploring the potential of gene therapy approaches  for the treatment of cancer. 

3、Combination therapy of MDSC checkpoint blockade  and other immunotherapies such as PD-1/PD-L1, CAR-T.

Despite the remarkable success and efficacy of ICB therapy against the PD-1/PD-L1 axis or CAR-T immunotherapy, it induces sustained responses in a sizeable minority of cancer patients due to the activation of immunosuppressive factors such as MDSCs. Blockade of the immunosuppressive function of MDSCs by targeting myeloid checkpoints like C/EBPβ, STAT3 and c-Rel is critical for successful cancer ICB or CAR-T therapy. Whether other MDSC checkpoints exist that can be targeted to treat cancer is not well established. By using single-cell transcriptomics,  my group hope to identify the specific populations of MDSCs that do not respond to cancer ICB or CAR-T therapy, and identify the specific MDSC checkpoints for treating cancer.

Ph.D. (Immunology), Sun Yat-sen University, Guangzhou, China, 2010-2013
Post-Doc. (Immunology), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China, 2014-2016

1/2020-Present: Associate Research Fellow (PI) –Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

1/2017- 12/2019: Assistant Research Fellow –Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

9/2014-12/2016: Post-Doc –Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

7/2013-8/2014: Deputy director of technology –Forevergen Biosciences Co., Ltd., Guangzhou, China

(#Co-first author,*Corresponding author)

1) Mengqi Zhang, Lulu Wang, Wan Liu, Tian Wang, Francesco De Sanctis, Lifang Zhu, Guizhong Zhang, Jian Cheng, Qin Cao, Jingying Zhou, Aldo Tagliabue, Vincenzo Bronte*, Dehong Yan*, Xianchun Wan*, Guang Yu*. Targeting inhibition of accumulation and function of myeloid-derived suppressor cells by artemisinin via PI3K/AKT, mTOR and MAPK pathways enhances anti-PD-L1 immunotherapy in melanoma and liver tumors. Journal of Immunology Research. 2022. Volume 2022, Article ID 2253436, 21 pages.（JCR Q2，IF4.818）

2)Adeleye O. Adeshakin# , Funmilayo O. Adeshakin# , Dehong Yan*, Xiaochun Wan*. Regulating Histone Deacetylase Signaling Pathways of Myeloid-Derived Suppressor Cells Enhanced T Cell-Based Immunotherapy. Frontiers in Immunology. 2022; 13:781660.（JCR Q1，IF7.561）

3) Lu-Lu Wang#, Dehong Yan#, Xue Tang, Mengqi Zhang, Shilin Liu, Ying Wang, Min Zhang, Guichi Zhou, Tonghui Li, Feifei Jiang, Xiaowen Chen, Feiqiu Wen, Sixi Liu*, Huirong Mai*. High Expression of BCL11A Predicts Poor Prognosis for Childhood MLL-r ALL. Frontiers in Oncology. 2021; 11: 755188.（JCR Q2，IF6.244）

4)Adeleye Oluwatosin Adeshakin, Funmilayo O. Adeshakin, Wan Liu, Hua Li, Dehong Yan*, Xiaochun Wan*. Lipidomics data showing the effect of lipofermata on myeloid-derived suppressor cells in the spleens of tumor-bearing mice. Data in Brief. 2021 April;35:106882.

5) Adeleye Oluwatosin Adeshakin, Wan Liu, Funmilayo O. Adeshakin, Lukman O. Afolabi, Mengqi Zhang, Guizhong Zhang, Lulu Wang, Zhihuan Li, Lilong Lin, Dehong Yan*, Xiaochun Wan*. Regulation of  ROS  in myeloid-derived suppressor cells through targeting fatty-acid transport protein 2 enhanced anti-PD-L1 tumor immunotherapy. Cellular Immunology. 2021 Jan 19; 362:104286.（JCR Q2，IF4.868）

6) Dehong Yan, Jinghui Wang, Honghong Sun, Ali Zamani, Honglin Zhang, Weihong Chen, Aifa Tang, Qingguo Ruan, Xiaolu Yang, Youhai H. Chen*, Xiaochun Wan*. TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis. Journal of Experimental Medicine. 2020 Feb 3; 217(2): e20182005. (Cover story, JCR Q1，IF14.307)

7) Adeleye O. Adeshakin#, Dehong Yan#, Mengqi Zhang, Lulu Wang, Funmilayo O. Adeshakin, Wan Liu, Xiaochun Wan*. Blockade of myeloid-derived suppressor cell function by valproic acid enhanced anti-PD-L1 tumor immunotherapy. Biochemical and Biophysical Research Communications. 2020 Feb 12;522(3):604-611.

8) Dehong Yan#, Adeleye O. Adeshakin#, Meichen Xu, Lukman O. Afolabi, Guizhong Zhang, Youhai H. Chen, Xiaochun Wan*. Lipid Metabolic Pathways Confer the Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor. Frontiers in Immunology. 2019; 10: 1399. （JCR Q1，IF7.561）

9) Dehong Yan, Quan Yang, Maohua Shi, Limei Zhong, Changyou Wu, Tao Meng, Huiyong Yin, Jie Zhou*. Polyunsaturated fatty acids promote the expansion of myeloid-derived suppressor cells by activating JAK2/STAT3 pathway. European Journal of Immunology. 2013 Nov;43(11):2943-55. （JCR Q2，IF5.532）

10) Dehong Yan#, Meichen Xu#, Jinghui Wang, Xiaochun Wan*. Research progresses on drug targets，immunomodulatory activity，and anti-tumor mechanisms of artemisinin and its analogues. Immunogical  Journal. 2018;34(8):713-720. (Chinese Journal)

11) Funmilayo O. Adeshakin, Adeleye O. Adeshakin , Zhao Liu , Jian Cheng, Pengchao Zhang, Dehong Yan , Guizhong Zhang *, Xiaochun Wan *.Targeting Oxidative Phosphorylation- Proteasome Activity in Extracellular Detached Cells Promotes Anoikis and Inhibits Metastasis. Life. 2022;12(1):42.

12) Lukman O Afolabi#, Jiacheng Bi#,Xuguang Li, Adeleye O. Adeshakin, Funmilayo O. Adeshakin, Haisi Wu, Dehong Yan, Liang Chen, XiaochunWan*. Synergistic Tumor Cytolysis by  NK Cells in Combination With a Pan-HDAC Inhibitor, Panobinostat. Frontiers in Immunology. 2021;12:701671.（JCR Q1，IF7.561）

13) Funmilayo O. Adeshakin, Adeleye O. Adeshakin, Zhao Liu, Xiaoxu Lu, Jian Cheng, Pengchao Zhang, Dehong Yan, Guizhong Zhang*, Xiaochun Wan*. Upregulation of V-ATPase by STAT3 Activation Promotes Anoikis Resistance and Tumor Metastasis. Journal of Cancer. 2021; 12(16):4819-4829.

14) Lukman O Afolabi#, Mariam O Afolabi#, Musbahu M Sani#, Wahab O Okunowo,  Dehong Yan,  Liang Chen,  Yaou Zhang*, XiaochunWan*. Exploiting the CRISPR‐Cas9 gene‐editing system for human cancers and immunotherapy. Clinical & Translational Immunology. 2021;10: e1286.（JCR Q2，IF6.161）

15) Funmilayo Oladunni Adeshakin, Adeleye Oluwatosin Adeshakin, Lukman Olalekan Afolabi, Dehong Yan, Guizhong Zhang* and Xiaochun Wan*. Mechanisms modulating anoikis resistance in cancer and the relevance of metabolic reprogramming. Frontiers in Oncology. 2021 Mar 29;11:626577. （JCR Q2，IF6.244）

16) Jian Cheng#, Zhao Liu#, Tian Deng, Zhen Lu, Maoxuan Liu, Xiaoxu Lu, Funmilayo O. Adeshakin, Dehong Yan, Guizhong Zhang*, Xiaochun Wan*. CD317 mediates immunocytolysis resistance by RICH2/cytoskeleton-dependent membrane protection. Molecular Immunology. 2020 Nov 19;S0161-5890(20)30531-9. （JCR Q2，IF4.407）

17) Oluwamuyiwa A. Ayanshina# , Adeleye O. Adeshakin#, Lukman O. Afolabi , Funmilayo O. Adeshakin, Ganiyu O. Alli-Balogun, Dehong Yan, Samuel Essien-Baidoo*, Xiaochun Wan*. Seasonal variations in Nigeria: understanding COVID-19 transmission dynamics and immune responses. Journal of Global Health Reports. 2020:e2020084.

18) Qian Chen, Dehong Yan, Qingmei Zhang , Guizhong Zhang, Meng Xia, Junxin Li, Wugen Zhan , Enyun Shen , Zhihuan Li , Lilong Lin , Youhai H Chen* , Xiaochun Wan*. Treatment of acetaminophen-induced liver failure by blocking the death checkpoint protein TRAIL. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2020 Jan 1;1866(1):165583. （JCR Q1，IF5.187）

19) Lulu Cui#，Jiacheng Bi#，Dehong Yan，Xiufeng Ye，Mingxing Zheng，Guang Yu*，Xiaochun Wan*. JSI-124 inhibits IgE production in an IgE B cell line. Biochemical and Biophysical Research Communications. 2017 Jan 29;483(1):669-673.

20) Aiping Qin#, Weiping Cai#, Ting Pan#, Kang Wu, Qiong Yang, Yufeng Liu, Nina Wang, Dehong Yan, Fengyu Hu, Pengle Guo, Xiaoping Chen, Ling Chen, Hui Zhang, Xiaoping Tang*, Jie Zhou*. Expansion of Monocytic Myeloid-Derived Suppressor Cells Dampens T Cell Function in HIV-1-Seropositive Individuals. Journal of Virology. 2013 Feb;87(3):1477-90. （JCR Q1，IF5.103）

21) Weiping Cai#, Aiping Qin#, Pengle Guo, Dehong Yan, Fengyu Hu, Qiong Yang, Min Xu, Yongshui Fu, Jie Zhou*, Xiaoping Tang*. Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients. Journal of Clinical Immunology. 2013 May;33(4):798-808. （JCR Q1，IF8.317）

Extramural funding

List your current and past grants (PI, Principle Investigator; PA, Participant)

1) Co-PI. National Key R&D Program of China (Grant 2021YFC3300100). Research on key technologies of independent development and controllable application of DNA inspection core equipments. 2021.12.01-2024.11.30; RMB 12,529,500.

2) PI. National Natural Science Foundation of China (Grant 82071772). Study on the molecular mechanism that TIPE2 mediates MDSC lipid metabolizing  reprogramming to regulate their functional polarization leading to tumor progression/degradation. 2021.01.01-2024.12.31; RMB 550,000.

3) PI. Basic and Applied Basic Research Foundation of Guangdong Province (Grant 2022A1515010070). Molecular mechanism of blocking MDSC immunosuppressive function mediated by DGAT1 and enhancing the efficacy of anti-PD-L1 antibody. 2022.01.01-2024.12.31; RMB 100,000.

4) PI. Shenzhen Basic Science Research Project (Grant JCYJ20190807161419228). Study on the mechanism of artemisinin  reversing tumor immunosuppressive microenvironment by targeting MDSCs. 2020.05.21-2023.05.31; RMB 300,000.

5) Co-PI. Basic and Applied Basic Research Foundation of Guangdong Province (Grant 2019A1515110359). Exploration of CAR-T immunocytotherapy  targeted hepatocellular carcinoma. 2020.01.01-2022.12.31; RMB 100,000.

6) PI. National Natural Science Foundation of China (Grant 81501356). Study on the molecular mechanism that PUFA reprogrammed lipid metabolism of MDSC and its role in tumor immune escape. 2016.01.01-2018.12.31; RMB 216,000.

7) PI. China Postdoctoral Science Foundation (Grant 2015M582447). Mechanism of tumor immune escape induced by PUFA reprogramming MDSC lipid metabolism. 2016.01.01-2017.12.31; RMB 50,000.

8) PI. Shenzhen Basic Science Research Project (Grant JCYJ20160229201353324). Molecular mechanism of tumor suppressor gene TIPE2 breaking tumor immune tolerance. 2016.06.23-2018.06.30; RMB 300,000.

9) PI. AAI Travel Grants for IUIS 2019.  USD  $2180.80.

10) PI. AAI Travel Grants for the 5th European Congress of Immunology 2018. USD  $2000.

11) PA. Shenzhen Basic Science Research Project (Grant JCYJ20150630114942293). Mechanism of DcR3 regulating EMT-dependent tumor metastasis. 2016.01.01-2017.12.31; RMB 300,000.

12) PA. Shenzhen Basic Science Research Project (Grant JCYJ20170413153158716).New targets for breast cancer therapy. 2017.06.28-2020.06.30; RMB 3,000,000.

13) PA. National Key R&D Program of China (Grant 2019YFA0906100). Design and construct a new generation of immune cells targeting solid tumor. 2020.01.01-2024.12.31; RMB 9,920,000.

AAI Early Career Faculty Grant，2021

AAI Travel Grants for IUIS 2019, 2019

AAI Travel Grants for the 5th European Congress of Immunology,  2018

Member, American Association of Immunologists, 2017-Present

Member, Guangdong Immunology Society, 2020-Present

Reviewer, OncoImmunology, 2020-Present

Reviewer, Basic & Clinical Pharmacology & Toxicology, 2020-Present

Reviewer, Frontiers in Genetics, 2020-Present

Reviewer, Frontiers in Immunology, 2022-Present

Reviewer, Cancer Immunology Immunotherapy, 2022-Present

Reviewer, Oxidative Medicine and Cellular Longevity, 2022-Present

Reviewer, Experimental Hematology & Oncology, 2022-Present

Reviewer, Scientific Reports, 2022-Present

Reviewer,  Life (Basel), 2022-Present