Lieping Chen, MD, PhD
Research & Publications
Biography
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Research Summary
My laboratory is interested in:
- T cell biology: Control of T cell response to antigens by cell surface receptors/ligands
- Cancer immunology: Mechanisms of tumor escape from immune attack in the tumor microenvironment
- Immunotherapy: Development of novel therapeutic approaches for human diseases (cancer, autoimmune diseases, inflammation etc.) based on our laboratory discoveries
Extensive Research Description
In 1992, Dr. Lieping Chen showed the first proof-of-concept study that the B7-CD28 family molecules could be targets for cancer immunotherapy. This study inspired subsequent research targeting the B7-CD28 family molecules for the treatment of human cancer.
In 1999, Dr. Chen first discovered a molecule he called B7-H1 (also known as PD-L1). He subsequently showed that PD-L1 is expressed by tumors and that its activity can cause T cell dysfunction, thus preventing T cells from eliminating cancer cells in the tumor microenvironment. Bringing these lines of inquiry full circle, Lieping later showed that PD-L1 is highly upregulated in a fraction of human cancers, and blocking the interaction between PD-1 and PD-L1 by monoclonal antibodies (mAbs) improved the immune system’s ability to eliminate tumors. Chen’s work provided a foundation for the subsequent development of anti-PD-L1/PD-1 mAb-based immunotherapies. Dr. Chen also initiated and facilitated the first-in-human clinical trial of anti-PD-1/PD-L1 mAbs for treating human cancer and developed PD-L1 staining as a biomarker for these treatments. His discoveries directly led to the development of anti-PD-1/PD-L1 antibody therapy against a broad spectrum of human cancers, which became the new standard for current cancer treatment.
Other findings made by Dr. Chen's laboratory include the development of an agonist antibody against the 4-1BB (also known as CD137) co-stimulatory pathway to costimulate and promote survival of effector T cells, leading to the elimination of established tumors in mouse models. These findings have since been developed and are now being evaluated in clinical trials for human cancer. Dr. Chen’s laboratory also discovered various molecular pathways with T cell costimulatory and coinhibitory functions and/or their applications in human disease treatment. These pathways include B7-H2 (ICOSL), B7-H3, B7-H4, B7-H5/CD28H, PD-1H (VISTA), TNFRSF19, RELT, LIGHT/HVEM, B7-H2/CD28/CTLA-4 (human), SALM5/HVEM, FGL1/LAG-3, Siglec-15, etc. Many of these findings are now being developed clinically for the treatment of human cancer, autoimmune diseases, and inflammation.
Coauthors
Research Interests
Immunotherapy; Inflammation; Medical Oncology; Neoplasms; Autoimmunity
Public Health Interests
Cancer; Immunology
Selected Publications
- Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunitiesKim TK, Vandsemb EN, Herbst RS, Chen L. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nature Reviews Drug Discovery 2022, 21: 529-540. PMID: 35701637, DOI: 10.1038/s41573-022-00493-5.
- The CD8α–PILRα interaction maintains CD8+ T cell quiescenceZheng L, Han X, Yao S, Zhu Y, Klement J, Wu S, Ji L, Zhu G, Cheng X, Tobiasova Z, Yu W, Huang B, Vesely MD, Wang J, Zhang J, Quinlan E, Chen L. The CD8α–PILRα interaction maintains CD8+ T cell quiescence. Science 2022, 376: 996-1001. PMID: 35617401, DOI: 10.1126/science.aaz8658.
- When immunotherapy meets surgery in non-small cell lung cancerHerbst RS, Wang M, Chen L. When immunotherapy meets surgery in non-small cell lung cancer. Cancer Cell 2022, 40: 603-605. PMID: 35660136, DOI: 10.1016/j.ccell.2022.05.010.
- Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapySun Y, Chen W, Torphy RJ, Yao S, Zhu G, Lin R, Lugano R, Miller EN, Fujiwara Y, Bian L, Zheng L, Anand S, Gao F, Zhang W, Ferrara SE, Goodspeed AE, Dimberg A, Wang XJ, Edil BH, Barnett CC, Schulick RD, Chen L, Zhu Y. Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy. Science Translational Medicine 2021, 13 PMID: 34321321, PMCID: PMC8749958, DOI: 10.1126/scitranslmed.abc8922.
- A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer ImmunotherapySanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.
- PD-1H (VISTA)–mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosusHan X, Vesely MD, Yang W, Sanmamed MF, Badri T, Alawa J, López-Giráldez F, Gaule P, Lee SW, Zhang JP, Nie X, Nassar A, Boto A, Flies DB, Zheng L, Kim TK, Moeckel GW, McNiff JM, Chen L. PD-1H (VISTA)–mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus. Science Translational Medicine 2019, 11 PMID: 31826980, DOI: 10.1126/scitranslmed.aax1159.
- Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapyWang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, Zhang J, Song C, Zarr M, Zhou X, Han X, Archer KA, O’Neill T, Herbst RS, Boto AN, Sanmamed MF, Langermann S, Rimm DL, Chen L. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nature Medicine 2019, 25: 656-666. PMID: 30833750, PMCID: PMC7175920, DOI: 10.1038/s41591-019-0374-x.
- Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J, Chen L, Chen Y, Zhu G, Yin W, Zheng L, Zhou T, Badri T, Yao S, Zhu S, Boto A, Sznol M, Melero I, Vignali DAA, Schalper K, Chen L. Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell 2018, 176: 334-347.e12. PMID: 30580966, PMCID: PMC6365968, DOI: 10.1016/j.cell.2018.11.010.
- A Paradigm Shift in Cancer Immunotherapy: From Enhancement to NormalizationSanmamed MF, Chen L. A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell 2018, 175: 313-326. PMID: 30290139, PMCID: PMC6538253, DOI: 10.1016/j.cell.2018.09.035.
- Classification of Advanced Human Cancers Based on Tumor Immunity in the MicroEnvironment (TIME) for Cancer ImmunotherapyZhang Y, Chen L. Classification of Advanced Human Cancers Based on Tumor Immunity in the MicroEnvironment (TIME) for Cancer Immunotherapy. JAMA Oncology 2016, 2: 1403-1404. PMID: 27490017, PMCID: PMC5492376, DOI: 10.1001/jamaoncol.2016.2450.