Personal profile

Chen Jun, Professor, PhD Supervisor, Zhongshan School of Medicine, Sun Yat-sen University. The youth project winner of the "Overseas High-level Talent Introduction Program" of the Organization Department of the CPC Central Committee, the young top talents of the "Pearl River Talent Program" of Guangdong Province, the young and middle-aged outstanding talents of Sun Yat-sen University's "Hundred Talents Program", and the outstanding scholars of Sun Yat-sen University's "Yixian Scholars Program". He received his bachelor's degree from Wuhan University in 2007, and his doctorate degree from the Institute of Biophysics, Chinese Academy of Sciences (University of Chinese Academy of Sciences) in 2013. He worked as a postdoctoral researcher at the Montreal Clinical Research Institute (IRCM) in Canada from 2013 to 2018, and joined Sun Yat-Sen University in 2018.
He has published many important results in Nature, Nature Cancer (2 articles), Cell Reports, Molecular Cancer, Cellular Oncology and other leading journals. Has applied for a number of international and Chinese patents in related fields. Obtained the "Tumor Immunity and Tumor Metabolism" project of the National Natural Science Foundation of China, the National Natural Science Foundation of China, the National Key Research and Development Project of the Ministry of Science and Technology (2), the Guangdong Natural Science Foundation Outstanding Youth Team Project, the Foundation of Guangzhou Basic and Applied Basic Research Project, Sun Yat-sen University Key Training Project for Young Teachers, and the Macao Science and Technology Project Development fund and other project support.
Subject specialty: Immunology

Scientific research direction

Malignant tumor is one of the biggest killers of human health, causing great burden and loss to the medical system. Tumor immunotherapy is currently the most promising approach to fighting cancer, was named Scientific Breakthrough of the Year in 2013 by Science magazine, and won the 2018 Nobel Prize in Medicine or Physiology. Tumor immunotherapy promotes or restores the anti-tumor activity of Immune cells by blocking the Immune Checkpoint Pathway on immune cells, and reactivates the patient's own immune system to fight cancer. A variety of new PD-1/PD-L1 monoclonal antibody drugs have been approved for tumor immunotherapy. These new drugs have achieved good clinical effect on a small number of patients with advanced cancer, but the current clinical indications only include a very limited part of non-small cell lung cancer, melanoma and lymphoma, and the average clinical response rate is only about 28%, and the vast majority of "cold tumor" patients have no effect. The efficacy of these drugs depends on the infiltration of killer CD8+ T cells (CTL) in tumor tissue. However, most "cold tumors" have less T-cell infiltration, which is one of the main reasons that PD-1 therapy does not respond to the vast majority of patients with "cold tumors."
However, the tumor microenvironment contains a large number of macrophages, and tumor immunotherapy targeting macrophages has great potential. The combination of macrophage therapy and T cell immunotherapy will be one of the most important directions of tumor immunotherapy. However, our understanding of the functional mechanism of macrophages in the tumor microenvironment and anti-tumor immunity is very insufficient, and further research is needed. Therefore, it is imperative to find new macrophage immune checkpoints and explore new mechanisms of anti-tumor immunity, and develop innovative tumor immunotherapy drugs to provide innovative targets and drug precursors for a new generation of multi-target and multi-protocol tumor immunotherapy.
At present, our work focuses on the regulatory mechanism of tumor immune microenvironment, new targets and new therapies for tumor immunotherapy. The main directions include: (1) the functional mechanism of CD47-SIRRP α macrophage checkpoint in tumor immunotherapy; (2) The discovery of novel immune checkpoints on macrophages and the development of related drugs; (3) Study on tumor immune microenvironment. There are already multiple original targets that are being translated into new drugs in the First in Class.
Macrophage CD47-SIRRP α immune checkpoint pathway (" Don't eat me "signal) is a promising new tumor immune target and research hotspot. However, the mechanism of phagocytosis receptors and "Eat me"  signaling in macrophages has not been revealed. We are the first in the world to identify the phagocytic receptor SLAMF7/Mac-1 complex of macrophages and the "Eat me" signal, revealing the mechanism of innate immunotumor immunotherapy (Nature, 2017, sole first author). At the same time, he was invited to publish a special review article in the prestigious journal Trend in Immunology (2018). We proposed SLAMF7 as a novel diagnostic biomarker for precision immunotherapy of tumors and applied for a PCT patent based on this, and the predicted indication was validated by multiple independent clinical trials (N. Engl. J. Med.2018, J. Clin. Oncol.2019).
We also found that the phagocytic pathway is altered in inflammatory pathology and its efficiency is dependent on CD11a/CD1c/CD8, providing a new explanation for immune diseases caused by macrophage dysfunction (Cell Reports, 2021, corresponding author).
Further, we discovered a combination regimen of CD47 antibody drugs for the treatment of solid tumors (J Leukocyte Biol, 2021, corresponding author) and obtained an authorized patent (granted patent: 202010636864.8).
Through single-cell sequencing and spatial transcriptomic sequencing of tumor specimens from more than 20 cases of brain glioma patients undergoing immunotherapy, we found that SIGLEC9-positive TAMs were enriched in tumors of brain glioma patients with poor immunotherapy efficacy, and the course of brain glioma in SiglecE knockout mice was significantly inhibited. Targeting SiglecE effectively activates anti-tumor immune response and remodeling of tumor microenvironment to effectively control the development of brain glioma (Nature Cancer, 2023, corresponding author).
Recently, we found that the patient's colorectal cancer tissue was enriched with SIRRP α+ macrophages by single-cell sequencing. The growth of multiple solid tumors in SIRP-α KO mice was significantly slowed, and this activity was independent of the traditional ligand of SIRP-α, CD47. The deletion of SIRRP α regulates the functional reprogramming of macrophages in the tumor microenvironment through the Btk/Syk/CCL8 signaling pathway, exerting the function of powerful antigen-presenting cells, thereby activating the downstream T cell immune response, and activating the anti-tumor immune response by a novel CD47-independent mechanism. (Nature Cancer, 2024, Corresponding author).
In addition, we report that CD43 molecules regulate the immune microenvironment of colorectal cancer (Cellular Oncology, 2023, cover article, corresponding author), Mon2 modulates the functional mechanisms of breast Cancer immunotherapy (Molecular Cancer, 2022, corresponding author) and HVEM molecules regulate immune escape in acute lymphoid leukemia (Cellular Oncology, 2024, corresponding author).

Academic work

1. Huang C., et al. Sirpα on tumor-associated myeloid cells restrains antitumor immunity in colorectal cancer independent of its interaction with CD47. Nature Cancer 2024; https://www.nature.com/articles/s43018-023-00691-z. (通讯作者) (Impact factor=23.2)
2. Mei, Y., et al. Siglec-9 acts as an immune-checkpoint molecule on macrophages in glioblastoma, restricting T-cell priming and immunotherapy response. Nature Cancer 2023; 4, 1273–129. (通讯作者) (Impact factor=23.2)
3. Wang XM., Chen J., and Jia GS. From dichotomy to diversity: deciphering the multifaceted roles of tumor-associated macrophages in cancer progression and therapy. Cancer Biology & Medicine 2023; 20230370; DOI: https://doi.org/10.20892/j.issn.2095-3941.2023.0370. (通讯作者)
4. Zhao ZN., et al. A Nanobody–Bioorthogonal Catalyst Conjugate Triggers Spatially Confined Prodrug Activation for Combinational Chemo-immunotherapy. Journal of Medical Chemistry 2023; 66, 17, 11951–11964. (通讯作者)
5. Feng YY., et al. SIRPα: A key player in innate immunity. European Journal of Immunology 2023; 53:2350375.（Invited Review）(通讯作者)
6. Li Yy., et al. Targeting CD43 optimizes cancer immunotherapy through reinvigorating antitumor immune response in colorectal cancer. Cellular Oncology 2023; 46: 777–791 (封面文章) (通讯作者)
7. Li Y., et al. Integrative analysis of CRISPR screening data uncovers new opportunities for optimizing cancer immunotherapy. Molecular Cancer 2022; 21:2. (通讯作者) (Impact factor=41.4)
8. Chen X., et al. Crystal structures of bat and human coronavirus ORF8 protein Ig-like domain provide insights into the diversity of immune responses. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2021.807134. (通讯作者)
9. Mao C., et al. Pan-cancer Analysis of GALNTs Expression Identifies a Prognostic of GALNTs Feature in Low Grade Glioma. Journal of Leukocyte Biology. 2022; 112:887–899. (通讯作者)
10. Tang Z., et al. Inflammatory macrophages exploit unconventional pro-phagocytic integrins for phagocytosis and anti-tumor immunity. Cell Reports. 2021. 37, 110111. (通讯作者) (Impact factor=9.99)
11. Li Y., et al. Identification of a novel immune signature for optimizing prognosis and treatment prediction in colorectal cancer. Aging. 2021; 13:25518-25549. (通讯作者)
12. Zhong, C. et al. Poly(I:C) enhances the efficacy of phagocytosis checkpoint blockade immunotherapy by inducing IL-6 production. Journal of Leukocyte Biology 2021; 110:1197–1208. (通讯作者)
13. Zhou, Z., et al., Structural Insight Reveals SARS-CoV-2 ORF7a as an Immunomodulating Factor for Human CD14+ Monocytes. iScience. 2021; 24, 102187. (通讯作者)
14. Zhong C., Chen, J.# CAR-T cells engineering with CCR6 exhibit superior anti-tumor efficacy. Science Bulletin. 2021; 66:755–756. (通讯作者) (Impact factor=20.5)
15. Chen J., et al. SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature. 2017; 544, 493-497. (唯一第一作者) (Impact factor=69.5)
16. Veillette A# and Chen J. SIRPα–CD47 Immune Checkpoint Blockade in Anticancer Therapy. Trends in Immunology. 2018; 39(3):173-184. (Impact factor=19.7)
17. Chen J. et al. The Endoplasmic Reticulum Adaptor Protein ERAdP Initiates NK Cell Activation via the Ubc13-Mediated NF-kB Pathway. The Journal of Immunology. 2015; 194,1292-1303. (第一作者)
18. Guo Y, et al. Valosin-containing protein cleavage by granzyme K accelerates an endoplasmic reticulum stress leading to caspase-independent cytotoxicity of target tumor cells. Journal of Immunology. 2010; 185(9): 5348-5359. (共同第一作者)

Scientific research project

1. Youth Project of "Overseas High-level Talent Introduction", Organization Department of the CPC Central Committee, 2018-2021, presided over.
2. "100 People Plan" Project, Sun Yat-sen University, 2018-2023, Host.
3. National Key Research and Development Project-1, 2019-2023, subject backbone, participation.
4. Key Training Project for Young Teachers, Sun Yat-sen University, 2019-2020, hosted.
5. Guangzhou Basic and Applied Basic Research Project, 2020-2023, Host.
6. "Pearl River Talent Plan" Young Top Talent of Guangdong Province, 2020-2025, host.
7. Macao Science and Technology Development Fund, 2020-2023, Participation.
8. 2020 Open Research Fund of Key Laboratory of Gene Function and Regulation, Ministry of Education, 2020-2021.
9. 2020 National Natural Surface Project, 2021-2024, Host.
10. National Key Research and Development Project-2, 2021-2025, Project leader.
11. 2022 National Nature Guide original exploration Program - "Tumor Immunity and Tumor Metabolism" project, 2022-2024, host.
12. 2024 Outstanding Youth Team Project of Guangdong Natural Science Foundation, 2024-2027, Core member.

Academic part-time job

Secretary of Party Branch, Vice president and Chairman of Youth Committee of Guangdong Immunology Society
Deputy editor of the international journal Cellular Oncology (District 1, Chinese Academy of Sciences)
Standing member of Youth Working Committee, Chinese Society of Immunology
Director of Immune-cell Biology Branch, Chinese Society for Cell Biology
Chinese Pathophysiological Society immunology Committee member and vice chairman of the Youth Committee
Member of the Professional Committee of Tumor biotherapy, Chinese Anticancer Association
Member of the Special Committee of Blood Physiology, Chinese Physiological Society