Zhibin Chen, Ph.D.
Assistant Professor of Microbiology and Immunology
Description of Research
Dr. Chen’s research interests focus on mechanisms of immune regulation and immune destruction in autoimmunity and antitumor immunity. In a long standing paradigm, the failure of the immune system to reject tumors is attributed largely to poor immunogenicity of tumor tissues. However, recent studies have demonstrated that antitumor responses can be readily generated but are dominantly suppressed by factors from both the host immune system and the tumors themselves, including prominent elements responsible for physiological immune tolerance, such as the cytotoxic T lymphocyte antigen 4 (CTLA4), the Foxp3-dependent regulatory T (Treg) cells, and the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Advances in cellular and molecular immunology have brought various concepts and ideas to cancer immunology, leading to breakthroughs in cancer immunotherapies that are tested in an expansion of clinical trials. These trials have generated promising results that may lead to the goal of curing cancers, but have also revealed many challenges that are difficult to address on the platform of clinical trials with human cancers. As exemplified in one of most successful trial venues in cancer immunotherapies, boosting antitumor immunity by CTLA4 blockade; a prominent issue that has emerged, is the entangling of autoimmunity toxicity and antitumor immunity. Dr. Chen’s group is developing novel animal models to dissect the autoimmunity implications in antitumor immunity. The focus is on the quantitative interactions among various immune tolerance elements including CTLA4, Treg cells, and IDO. These elements may be hijacked by tumor cells and form a nexus of immune suppression in the microenvironment of tumor tissues, presenting a major hurdle for immune destruction of tumors. A better understanding of the local immunosuppressive mechanisms at the tumor site will help therapeutic targeting to overcome the local immunosuppression at the tumor sites while minimizing off-target adverse immune damage.
Highlights
- The quantitative biology of CTLA4 in immune regulation and destruction. The quantitative variations of CTLA4 have been associated with human autoimmunity, cancer occurrence, and both the autoimmune toxicity and therapeutic efficacy in cancer immunotherapy. With a novel approach of lentiviral RNAi transgenesis, Dr. Chen and his colleagues have found that subtle quantitative variations of CTLA4 levels regulate tissue-specific immune damage.
- The role of Treg cells in local immunosuppression in the microenvironment of tumor tissues. Dr. Chen and his colleagues have found that Treg cells play a critical role in local inflammatory settings to suppress immune destruction of both normal and malignant tissues.
- Lentiviral RNAi transgenesis approach to study the quantitative impact of genes in chronic disease models. Dr. Chen is among the few investigators in the world who have had successful experience with this approach. In an era of genomics and genetics, discoveries often manifest as quantitative variations of gene expressions or gene dosage effects. Lentiviral RNAi transgenesis is useful in bridging the genomic and genetic findings to immunobiology and potential immunotherapies.
- Studies of autoimmune mechanisms in antitumor immunity revealed tumor as an "immuneprivileged self"
Selected Cancer-Related Publications
Programs
Collaborating in the Multidisciplinary Research Program(s):