Peiwen Chen Laboratory

Research

The Chen laboratory studies the molecular and biological processes governing the development of brain malignancies, including primary (e.g., glioblastoma) and metastatic (tumors originating from other locations in the body, such as breast cancer) brain cancers. Specifically, the laboratory focuses on characterizing the molecular mechanisms governing the symbiotic interactions between cancer cells/cancer stem cells and immune cells (including macrophages, microglia, myeloid-derived suppressor cells and T cells) in brain malignancies, and how such heterotypic signaling enables a tumor-promoting ecosystem and informs therapeutic strategies intercepting these co-dependencies.

The laboratory takes an integrated strategy combining gain- and loss-of-function approaches, in vitro and in vivo systems, as well as proteomic and transcriptomic analyses to:

(1) study how specific tumor context, such as genetic alternations (e.g., tumor suppressor gene mutation/deletion and oncogene amplification/mutation), epigenetic modifications, circadian dysregulation, and metabolic changes of cancer cells and cancer stem cells can shape an immunosuppressive tumor microenvironment by regulating the infiltration and polarization of myeloid cells (e.g., macrophages, microglia, and myeloid-derived suppressor cells).

(2) elucidate the mechanisms for how these infiltrated and polarized myeloid cells affect tumor growth, brain metastasis, and T cell-mediated anti-tumor immunity.

(3) understand how this tumor-immune cell symbiosis affects the effectiveness of cancer therapies (e.g., immunotherapy, anti-angiogenic therapy, and conventional therapies), thus developing novel and effective combination therapies. Our mission is to uncover novel mechanisms governing the development and progression of brain malignancies (including primary and metastatic brain cancers) and offer new therapeutic strategies for patients with these diseases. 

Selected Publications

View publications for Peiwen Chen, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)

Selected Research Articles: 

• Pang L, Guo S, Huang Y, Khan F, Liu Y, Zhou F, Lathia JD, and Chen P# (2025) Targeting legumain-mediated cell-cell interaction sensitizes glioblastoma to immunotherapy in preclinical models. Journal of Clinical Investigation doi:10.1172/JCI186034.
• Khan F, Lin Y, Ali H, Pang L, Dunterman M, Hsu WH, Frenis K, Rowe RG, Wainwright DA, McCortney K, Horbinski C, Lesniak MS and Chen P# (2024) LDHA-regulated tumor-macrophage symbiosis promotes glioblastoma progression. Nature Communications 15(1):1987. doi: 10.1038/s41467-024-46193-z.
• Liu Y, Wu J, Najem H, Lin Y, Pang L, Khan F, Zhou F, Ali H, Heimberger AB and Chen P# (2024) Dual targeting macrophages and microglia is a therapeutic vulnerability in models of PTEN-deficient glioblastoma. Journal of Clinical Investigation 134(22):e178628. doi: 10.1172/JCI178628.
• Pang L*, Dunterman M*, Guo S, Khan F, Liu Y, Taefi E, Bahrami A, Geula C, Hsu WH, Horbinski C, James CD and Chen P# (2023) Kunitz-type protease inhibitor TFPI2 remodels stemness and immunosuppressive tumor microenvironment in glioblastoma. Nature Immunology 24(10):1654-1670. (Cover article).
• Pang L*, Guo S*, Khan F*, Dunterman M, Ali H, Liu Y, Huang Y and Chen P# (2023) Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma. Cell Reports Medicine 4(11):101238. doi: 10.1016/j.xcrm.2023.101238.
• Pang L*, Dunterman M*, Xuan W, Gonzalez A, Lin Y, Hsu WH, Khan F, Hagan RS, Muller WA, Heimberger AB and Chen P# (2023) Circadian Regulator CLOCK Promotes Tumor Angiogenesis in Glioblastoma. Cell Reports 42 (2), 112127.
• Xuan W, Hsu WH, Khan F, Dunterman M, Pang L, Wainwright DA, Ahmed AU, Heimberger AB, Lesniak MS and Chen P# (2022) Circadian Regulator CLOCK Drives Immunosuppression in GBM. Cancer Immunology Research 10(6):770-784.

Selected Review Articles:

• Pang L*,  Huang Y*, Huang-Gao J and Chen P# (2025) Protease Regulation of Tumor-Immune Cell Symbiosis. Trends in Cancer 10.1016/j.trecan.2025.02.004.
• Liu Y*, Ali H*, Khan F, Pang L and Chen P# (2024) Epigenetic regulation of tumor-immune symbiosis in glioma. Trends in Molecular Medicine 30(5):429-442. (Cover article).
• Pang L*, Zhou F*, Liu Y, Ali H, Khan F, Heimberger AB and Chen P# (2024) Epigenetic regulation of tumor immunity. Journal of Clinical Investigation 134(12):e178540.
• Liu Y*, Zhou F*, Ali H, Lathia JD and Chen P# (2024) Immunotherapy for glioblastoma: Current state, challenges, and future perspectives. Cellular & Molecular Immunology (12):1354-1375.
• Pang L, Zhou F and Chen P# (2024) Lipid-laden macrophages recycle myelin to feed glioblastoma. Cancer Research 84(22):3712-3714.
• Chen P# (2023) TFPI2 is key for cancer stem cell–microglia symbiosis in glioblastoma. Nature Immunology 24(10): 1612-1613.
• Khan F*, Pang L*, Dunterman M, Lesniak MS, Heimberger AB and Chen P# (2023) Macrophages and microglia in glioblastoma: heteroge­­neity, plasticity, and therapy. Journal of Clinical Investigation 133(1):e163446.
• Pang L, Khan F, Heimberger AB and Chen P# (2022) Mechanism and Therapeutic Potential of Tumor-Immune Symbiosis in Glioblastoma. Trends in Cancer 8(10):839-854. (Cover article).
• Pang L, Khan F, Dunterman M and Chen P# (2022) Pharmacological Targeting of the Tumor-Immune Symbiosis in Glioblastoma. Trends in Pharmacological Sciences 43(8): 686–700.
• Xuan W*, Khan F*, James CD, Heimberger AB, Lesniak MJ and Chen P# (2021) Circadian Regulation of Cancer Cell and Tumor Microenvironment Crosstalk. Trends in Cell Biology 31(11): 940–950. (Cover article)
• Xuan W, Lesniak MJ, James CD, Heimberger AB and Chen P# (2021) Context-Dependent Glioblastoma-Macrophage/microglia Symbiosis and Associated Mechanisms. Trends in Immunology 42(4):280–292. (Cover article)