Identification of both MHC class I and II restricted antigens has provided opportunities to develop more effective cancer vaccines, however, current immunotherapy strategies with tumor antigens are relatively ineffective and have not produced compelling evidence of any durable therapeutic benefits. Recent studies suggest that inflammatory Th17 cells and innate immunity at tumor sites may promote rather than inhibit cancer development and progression. Moreover, CD4+ regulatory T (Treg) cells at tumor sites potently suppress the CD4+ and CD8+ T-cell responses elicited by vaccination, thus promoting tumor growth. These studies suggest that understanding of the interplay between immune cells and tumor cells is a critical step to develop more effective cancer therapy. The underlying rationale is that inflammation is a major driving force in the pathogenesis of many types of cancer, including colorectal cancer and viral infection-associated malignancies. The delicate and dynamic balance among antitumor immunity, inflammatory CD4+ Th17 cells and immune suppressive cells may be important factor in tumor elimination, development and progression. Despite the importance of inflammatory cytokines and CD4+ Th17 cells in cancer, their role and regulatory mechanisms in cancer remain controversial. We therefore hypothesize that innate immune signaling is critical in the control of inflammation, which in turn modulates adaptive immunity and CD4+ Th17 cell differentiation. Thus, identification of key innate immune signaling molecules that control inflammation and Th17 differentiation will be critical for us to define the role of inflammation and Th17 cells in inflammation-associated cancer development and to dissect molecular mechanisms by which inflammatory cytokines and Th17 cells directly or indirectly modulate tumor development. To test our central hypothesis, we propose three aims: 1) To determine whether NLRC5 and TAK1 can modulate key proinflammatory cytokines and Th17 cells in vivo;2) To define the function of inflammatory cytokines and Th17 cells in cancer development;3) To enhance antitumor immunity by manipulating innate signaling molecules, Th17 and Treg cells. A favorable outcome would open new opportunities for treating cancer and other immune diseases through regulating these inflammation and subsets of CD4+ T cells.
Immunotherapy is a promising treatment for cancer patients, but current strategies are relatively ineffective, mainly due to incomplete understanding of knowledge of the interplay between immune cells and tumor cells. The goal of this project is to understand the role and mechanisms of inflammation and Th17 cells in the tumor microenvironment, which aids in developing more effective strategies for cancer immunotherapy.
|Zhu, Motao; Ding, Xilai; Zhao, Ruifang et al. (2018) Co-delivery of tumor antigen and dual toll-like receptor ligands into dendritic cell by silicon microparticle enables efficient immunotherapy against melanoma. J Control Release 272:72-82|
|Yu, Xiao; Du, Yang; Cai, Chunmei et al. (2018) Inflammasome activation negatively regulates MyD88-IRF7 type I IFN signaling and anti-malaria immunity. Nat Commun 9:4964|
|Du, Yang; Duan, Tianhao; Feng, Yanchun et al. (2018) LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation. EMBO J 37:351-366|
|Xia, Lu; Wu, Jian; Pattaradilokrat, Sittiporn et al. (2018) Detection of host pathways universally inhibited after Plasmodium yoelii infection for immune intervention. Sci Rep 8:15280|
|Ning, Bo; Zhao, Wei; Qian, Chen et al. (2017) USP26 functions as a negative regulator of cellular reprogramming by stabilising PRC1 complex components. Nat Commun 8:349|
|Zhang, Jindong; Zhang, Chuanxia; Cui, Jun et al. (2017) TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination. Cell Death Dis 8:e2831|
|Wang, Rong-Fu; Wang, Helen Y (2017) Immune targets and neoantigens for cancer immunotherapy and precision medicine. Cell Res 27:11-37|
|Sheng, Si Yuan; Gu, Yong; Lu, Chuan Gang et al. (2017) The distribution and function of human memory T cell subsets in lung cancer. Immunol Res 65:639-650|
|Cai, Baowei; Wu, Jian; Yu, Xiao et al. (2017) FOSL1 Inhibits Type I Interferon Responses to Malaria and Viral Infections by Blocking TBK1 and TRAF3/TRIF Interactions. MBio 8:|
|Jin, Shouheng; Tian, Shuo; Chen, Yamei et al. (2016) USP19 modulates autophagy and antiviral immune responses by deubiquitinating Beclin-1. EMBO J 35:866-80|
Showing the most recent 10 out of 37 publications