Visiting Professor in Cancer Immunotherapy
- United Technologies Corporation Professor in Cancer Research and Professor of Immunobiology, of Dermatology and of Medicine (Medical Oncology), Yale School of Medicine, U.S.
- Co-Leader, Cancer Immunology Program, Yale Cancer Center
I am an immunologist interested in cell surface proteins that control lymphocyte functions and also translate my laboratory findings to treat human diseases including cancer, autoimmune diseases and inflammation.
In 1992, my laboratory showed the first proof-of-concept study that the B7-CD28 family molecules could be targeted for cancer immunotherapy. In 1999, we were the first to discover PD-L1 (originally termed B7-H1), and subsequently showed that PD-L1 is expressed by tumours and that its activity can cause T cell dysfunction, thus preventing T cells from eliminating cancer cells. We went on to show that blocking the interaction between PD-1 and PD-L1 by monoclonal antibodies improved the immune system’s ability to eliminate tumours. This work provided an important foundation for the subsequent development of immunotherapies designed to block this pathway, and thereby enable more effective immune responses against cancer. I also initiated and helped organise the first-in-human clinical trial of anti-PD-1 monoclonal antibody for treating human cancer in 2006 and developed PD-L1 staining as a biomarker. Our discoveries directly led to the development of anti-PD-1/PD-L1 antibody therapy against a broad spectrum of human cancers and this therapy has become a new standard for cancer treatment.
Other important breakthroughs made by my laboratory include the development of an agonist antibody against the 4-1BB co-stimulatory pathway, also known as CD137. Multiple 4-1BB-targeting antibodies have since been developed and are now being evaluated in clinical trials for a variety of cancer types. My laboratory also discovered various molecular pathways with T cell costimulatory and coinhibitory functions and/or their applications in human disease treatment.
I became a Visiting Professor at the Ludwig Institute for Cancer Research, University of Oxford in 2021.
Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L. Nature Medicine 2002, 8(8):793-800.
B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Dong H, Zhu G, Tamada K, Chen L. Nature Medicine 1999, 5(12):1365-9.
Molecular mechanisms of T cell co-stimulation and co-inhibition. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nature Reviews Immunology 2013, 13:227-42.
Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. Chen L, Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. The Journal of Clinical Investigation 2015, 125:3384-91.
A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Sanmamed MF, Chen L. A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell 2018, 175:313-326.