Hui Qiao

Bio: Hui Qiao is an academic researcher from University of Virginia. The author has contributed to research in topics: Immune tolerance & Cytotoxic T cell. The author has an hindex of 7, co-authored 8 publications receiving 625 citations. Previous affiliations of Hui Qiao include Georgia Regents University.

Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation

Abstract: Peripheral immune tolerance is generally thought to result from cross-presentation of tissue-derived proteins by quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative selection, leading to anergy or deletion. Recently, we and others have implicated the lymph node (LN) stroma in mediating CD8 T cell peripheral tolerance. We demonstrate that LN-resident lymphatic endothelial cells express multiple peripheral tissue antigens (PTAs) independent of the autoimmune regulator (Aire). They directly present an epitope derived from one of these, the melanocyte-specific protein tyrosinase, to tyrosinase-specific CD8 T cells, leading to their deletion. We also show that other LN stromal subpopulations express distinct PTAs by mechanisms that vary in their Aire dependence. These results establish lymphatic endothelial cells, and potentially other LN-resident cells, as systemic mediators of peripheral immune tolerance.

Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance

Abstract: Autoimmune responses to meiotic germ cell antigens (MGCA) that are expressed on sperm and testis occur in human infertility and after vasectomy. Many MGCA are also expressed as cancer/testis antigens (CTA) in human cancers, but the tolerance status of MGCA has not been investigated. MGCA are considered to be uniformly immunogenic and nontolerogenic, and the prevailing view posits that MGCA are sequestered behind the Sertoli cell barrier in seminiferous tubules. Here, we have shown that only some murine MGCA are sequestered. Nonsequestered MCGA (NS-MGCA) egressed from normal tubules, as evidenced by their ability to interact with systemically injected antibodies and form localized immune complexes outside the Sertoli cell barrier. NS-MGCA derived from cell fragments that were discarded by spermatids during spermiation. They egressed as cargo in residual bodies and maintained Treg-dependent physiological tolerance. In contrast, sequestered MGCA (S-MGCA) were undetectable in residual bodies and were nontolerogenic. Unlike postvasectomy autoantibodies, which have been shown to mainly target S-MGCA, autoantibodies produced by normal mice with transient Treg depletion that developed autoimmune orchitis exclusively targeted NS-MGCA. We conclude that spermiation, a physiological checkpoint in spermatogenesis, determines the egress and tolerogenicity of MGCA. Our findings will affect target antigen selection in testis and sperm autoimmunity and the immune responses to CTA in male cancer patients.

Cutaneous Exposure to Clinically Relevant Lone Star Ticks Promotes IgE Production and Hypersensitivity through CD4+ T Cell- and MyD88-Dependent Pathways in Mice.

Abstract: Tick-borne allergies are a growing public health concern and have been associated with the induction of IgE-mediated food allergy to red meat. However, despite the increasing prevalence of tick bite-induced allergies, the mechanisms by which cutaneous exposure to ticks leads to sensitization and the production of IgE Abs are poorly understood. To address this question, an in vivo approach was used to characterize the IgE response to lone star tick proteins administered through the skin of mice. The results demonstrated that tick sensitization and challenge induced a robust production of IgE Abs and supported a role for IgE-mediated hypersensitivity reactions in sensitized animals following oral administration of meat. The induction of IgE responses was dependent on cognate CD4+ T cell help during both the sensitization phase and challenge phase with cutaneous tick exposure. In addition, IgE production was dependent on B cell-intrinsic MyD88 expression, suggesting an important role for TLR signaling in B cells to induce IgE responses to tick proteins. This model of tick-induced IgE responses could be used to study the factors within tick bites that cause allergies and to investigate how sensitization to food Ags occurs through the skin that leads to IgE production.

Cross-presentation by dendritic cells.

Abstract: The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8(+) T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. Here, we summarize recent advances in our understanding of the intracellular mechanisms of cross-presentation and discuss its role in immunity and tolerance in the context of specialization between DC subsets. Finally, we review current strategies to use cross-presentation for immunotherapy.

The lymphatic vasculature in disease

Abstract: Blood vessels form a closed circulatory system, whereas lymphatic vessels form a one-way conduit for tissue fluid and leukocytes. In most vertebrates, the main function of lymphatic vessels is to collect excess protein-rich fluid that has extravasated from blood vessels and transport it back into the blood circulation. Lymphatic vessels have an important immune surveillance function, as they import various antigens and activated antigen-presenting cells into the lymph nodes and export immune effector cells and humoral response factors into the blood circulation. Defects in lymphatic function can lead to lymph accumulation in tissues, dampened immune responses, connective tissue and fat accumulation, and tissue swelling known as lymphedema. This review highlights the most recent developments in lymphatic biology and how the lymphatic system contributes to the pathogenesis of various diseases involving immune and inflammatory responses and its role in disseminating tumor cells.

Immunological hallmarks of stromal cells in the tumour microenvironment

Abstract: A dynamic and mutualistic interaction between tumour cells and the surrounding stroma promotes the initiation, progression, metastasis and chemoresistance of solid tumours. Far less understood is the relationship between the stroma and tumour-infiltrating leukocytes; however, emerging evidence suggests that the stromal compartment can shape antitumour immunity and responsiveness to immunotherapy. Thus, there is growing interest in elucidating the immunomodulatory roles of the stroma that evolve within the tumour microenvironment. In this Review, we discuss the evidence that stromal determinants interact with leukocytes and influence antitumour immunity, with emphasis on the immunological attributes of stromal cells that may foster their protumorigenic function.

Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes

Abstract: Purpose: Retrospective analysis of irAEs in melanoma patients treated with nivolumab. Experimental Design: Data were pooled from 148 patients (33 resected, 115 unresectable) treated with nivolumab plus peptide vaccine or nivolumab alone every 2 weeks for 12 weeks. Patients with stable disease or regression received an additional 12-week cycle, then nivolumab alone every 12 weeks for up to 2 additional years. Frequency, grade, and characteristics of immune-related adverse events (irAE) were analyzed. A 12-week landmark survival analysis using a multivariate time-dependent Cox proportional hazard model assessed difference in overall survival (OS) in the presence or absence of irAEs. Results: IrAEs of any grade were observed in 68.2% of patients (101 of 148). Grade III/IV irAEs were infrequent: 3 (2%) had grade III rash, 2 (1.35%) had asymptomatic grade III elevation in amylase/lipase, and 2 (1.35%) had grade III colitis. A statistically significant OS difference was noted among patients with any grade of irAE versus those without ( P ≤ 0.001), and OS benefit was noted in patients who reported three or more irAE events ( P ≤ 0.001). Subset analyses showed statistically significant OS differences with rash [ P = 0.001; HR, 0.423; 95% confidence interval (CI), 0.243–0.735] and vitiligo ( P = 0.012; HR, 0.184; 95% CI, 0.036–0.94). Rash and vitiligo also correlated with statistically significant OS differences in patients with metastatic disease ( P = 0.004 and P = 0.028, respectively). No significant survival differences were seen with other irAEs (endocrinopathies, colitis, or pneumonitis). Conclusions: Cutaneous irAEs are associated with improved survival in melanoma patients treated with nivolumab, and clinical benefit should be validated in larger prospective analyses. Clin Cancer Res; 22(4); 886–94. ©2015 AACR .

Lymphangiogenesis and lymphatic vessel remodelling in cancer

Abstract: The generation of new lymphatic vessels through lymphangiogenesis and the remodelling of existing lymphatics are thought to be important steps in cancer metastasis. The past decade has been exciting in terms of research into the molecular and cellular biology of lymphatic vessels in cancer, and it has been shown that the molecular control of tumour lymphangiogenesis has similarities to that of tumour angiogenesis. Nevertheless, there are significant mechanistic differences between these biological processes. We are now developing a greater understanding of the specific roles of distinct lymphatic vessel subtypes in cancer, and this provides opportunities to improve diagnostic and therapeutic approaches that aim to restrict the progression of cancer.