The long-term goal of the Laboratory of Cancer Immunobiology, led by Hong-Ming Hu, Ph.D., is to understand how the immune system senses tumor cells and develop effective cancer vaccines and immunotherapy strategies. The therapeutic cancer vaccine requires activation and expansion of therapeutic effector T cells in vivo to levels above the threshold required for tumor eradication and prevention of recurrence in tumor-bearing hosts. For most bacterial and viral infections, the robust innate and adaptive immune responses generally result in control of infection and development of a strong memory response. In contrast, for patients with cancer, the host immune system often fails to control the growth of cancer despite the fact that tumor cells replicate at a much slower rate than bacteria and viruses.
The major differences between the immunology of infection and tumors include the following: tumor cells lack strong antigens and, as compared to infections, tumor cells are sensed differently by innate immune system, which orchestrates the subsequent adaptive immune response. The Laboratory of Cancer Immunobiology investigates how tumor cells, live or dead, are sensed by innate immunity and how tumor antigens are cross-presented by host professional antigen presenting cells. Better understanding the mechanisms of early stage of immune recognition of tumor cells would lead to design novel cancer vaccines and immunotherapy strategies.
Current Projects
Tumor cells contain a large array of short-lived proteins that are ignored by a host immune system because they are rapidly degraded and disposed, thus they could not be cross-presented by host dendritic cells and are ignored by the host immune system. Our hypothesis is that these short-lived proteins could elicit strong tumor-specific immune responses when they are cross-presented by mature dendritic cells in a sufficient quantity if their degradation could be prevented. Preliminary studies in our laboratory have discovered that tumor cells are actively blebbing (Zeiosis) when they are treated with proteasome inhibitors. We refer to these zeiotic blebs as "DRibbles" because they contain ubiquitinated proteins possibly derived from defective ribosomal products (DRiPs) or other short-lived proteins (DRiPs in Blebs). DRibbles have induced a strong tumor-specific T-cell immunity and mediated tumor regression in several tumor models. Currently, we are working to determine the underlining mechanisms that enable DRibbles to induce a strong therapeutic T-cell mediated antitumor immunity in tumor-bearing mice as a preliminary step in developing immune-based therapies for human cancers.
Recently we demonstrated that autophagosomes are a major component of DRibbles and macroautophagy of tumor cells is critical for efficient cross-presentation of tumor-associated antigens.
Based on our findings and published literature from other scientists, we hypothesized that autophagic cell death tumor cells represents an immunogenic death pathway to increase antitumor immune responses. Consistent with this hypothesis, we recently found that autophagosomes express ligands for pattern recognition receptor, clec9a, whose expression is restricted to a subset of dendritic cells specialized in cross-presentation of cell-associated antigens.
In collaboration with
Jun Jiao, Ph.D., of Portland State University, we are developing new nanomaterials that could deliver agents into tumors to induce autophagic cell death and immune adjuvants.
Current Research Collaborations
Melanoma
Exploiting Lymphopenia to Augment the Adoptive Immunotherapy of Melanoma Patients
- Clinical:
- Walter J. Urba, M.D., Ph.D., director cancer research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
- Lab:
Adoptive Cellular Therapy in Melanoma
- Clinical:
- Walter J. Urba, M.D., Ph.D., director cancer research. Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
- Brendan Curti, M.D., director of genitourinary cancer research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
- Lab:
- Keith Bahjat, Ph.D., Laboratory of Immunological Monitoring, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
NSCLC
Clinical Trial of Dribble Vaccine in NSCLC
- Clinical:
- Walter J. Urba, M.D., Ph.D., director cancer research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
- Lab:
- Bernard A. Fox, Ph.D., Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
- Keith Bahjat, Ph.D., Laboratory of Immunological Monitoring, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
Liver Cancer
Development of therapeutic vaccines for HBV or HCV related hepatitis and hepatocellular carcinomas (HCC)
- Clinical:
- Todd Crocenzi, M.D., director of gastrointestinal Oncology Research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
Full List of Publications
Laboratory Team
Hong-Ming Hu, Ph.D.
Yuhuan Li, Ph.D.
Erik LeShane, Ph.D.
Shu Su, M.D., Ph.D.
Zhi Hua Cui
Laboratory Alumni
Yiwei Chu, M.D.
Min Fang, Ph.D.
Peter Hao, M.D.
Rui Li, M.D., Ph.D.
Ashling O'hara, M.S.
Puiyi Pang, M.S.
Lixin Wang, Ph.D.
Guojun Yang, M.D.