Yiping Yang

Overview:

The goal of Dr. Yang’s laboratory is to understand the molecular and cellular mechanisms leading to the generation of potent and long-lasting anti-tumor immunity, and to develop effective gene immunotherapeutic strategies for treating cancer. Furthermore, rational pre-clinical approaches will be tested in clinical trials in patients with Epstein-Barr virus (EBV)-related malignancies. Specifically, we focus on the following areas:

1. Innate Immunity to Viruses. Recombinant vaccinia virus and adenovirus have been developed as potent vaccine vehicles for treating cancer and infectious diseases. Recent studies have shown that the unique potency of these viruses lies in their effective activation of the innate immune system. How these viruses activate the innate immune system remains largely unknown. We have been interested in the role of pattern-recognition receptors including Toll-like receptors (TLRs)in innate immune recognition of these viruses as well as their signaling pathways. In addition, we are investigating the role of innate immune cells such as natural killer (NK) cells in innate and adaptive immune responses to these viruses. A full understanding of these processes will help us design effective vaccine strategies.

2. T Cell Memory. Eliciting long-lived memory T cell response is an ultimate goal of vaccination to provide long-term immunity against cancer. However, it is not clear what controls the formation of long-lived memory T cells. The understanding of mechanisms underlying memory T cell formation will provide important insights into the design of effective vaccines for treating cancer.

3. Regulatory T Cell Biology. Accumulating evidence has shown that the immunosuppressive CD4+CD25+Foxp3+ regulatory T cells (TReg) play a critical role in the suppression of anti-tumor immunity. However, little is known about how TReg suppress T cell activation in vivo. Delineation of mechanisms underlying TReg-mediated suppression in vivo will help develop strategies to overcome TReg-mediated suppression in favor of boosting anti-tumor immunity.

4. Immunotherapy for EBV-associated Malignancies. Clinically, EBV-associated malignancies such as Hodgkin’s lymphoma offer a unique model to explore antigen-defined immunotherapy approaches because EBV-derived tumor antigens are specific for tumor cells only. Using this clinical model, we will test the utility of rational strategies identified in our preclinical models.

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Professor of Immunology

Immunology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1985

Zhejiang University (China)

Ph.D. 1993

University of Michigan at Ann Arbor

Residency, General Internal Medicine

University of Pennsylvania School of Medicine

Fellowship, Medical Oncology

Johns Hopkins University School of Medicine

Grants:

Role of hedgehog signaling in tumor-associated macrophage polarization

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

T memory stem cells in cancer

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Novel Strategies for Cancer Immunotherapy in Stem Cell Transplant

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Role of Endogenous Toll-Like Receptor Ligands in Allospecific T Cell Activation

Administered By
Surgery, Abdominal Transplant Surgery
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Role of inflammation in cancer progression

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

PD-L1 serves as a double agent in separating GVL from GVHD.

Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative treatment for a variety of hematologic malignancies due to the well-recognized graft-versus-leukemia/lymphoma (GVL) effect that is mediated by donor-derived alloreactive T cells. However, graft-versus-host disease (GVHD) is mediated by the same T cells and remains a significant clinical problem associated with substantial morbidity and mortality. In this issue of the JCI, Ni and colleagues used several murine models of GVHD to evaluate the effect of CD4+ T cell depletion on GVL versus GVHD and revealed that depletion of CD4+ T cells leads to the upregulation of PD-L1 by recipient tissues and donor CD8+ T cells. Interaction of PD-L1 with PD-1 in GVHD-targeted tissues resulted in CD8+ T cell exhaustion and apoptosis, thereby preventing GVHD, whereas PD-L1 interactions with CD80 in lymphoid tissue promoted CD8+ T cell survival and expansion, thereby enhancing the GVL response. By separating these seemingly similar alloreactive T cell responses based on the context of interaction, the results of this study may lay the groundwork for the development of effective clinical strategies to enhance GVL while minimizing GVHD following allogeneic HCT.
Authors
Brennan, TV; Yang, Y
MLA Citation
Brennan, Todd V., and Yiping Yang. “PD-L1 serves as a double agent in separating GVL from GVHD..” J Clin Invest, vol. 127, no. 5, May 2017, pp. 1627–30. Pubmed, doi:10.1172/JCI94196.
URI
https://scholars.duke.edu/individual/pub1252987
PMID
28414300
Source
pubmed
Published In
J Clin Invest
Volume
127
Published Date
Start Page
1627
End Page
1630
DOI
10.1172/JCI94196

Cancer immunotherapy: harnessing the immune system to battle cancer.

The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer immunotherapy. These successes also underscore the importance of understanding basic tumor immunology for successful clinical translation in treating patients with cancer. The Reviews in this Review Series focus on current developments in cancer immunotherapy, highlight recent advances in our understanding of basic aspects of tumor immunology, and suggest how these insights can lead to the development of new immunotherapeutic strategies.
Authors
MLA Citation
Yang, Yiping. “Cancer immunotherapy: harnessing the immune system to battle cancer..” J Clin Invest, vol. 125, no. 9, Sept. 2015, pp. 3335–37. Pubmed, doi:10.1172/JCI83871.
URI
https://scholars.duke.edu/individual/pub1099160
PMID
26325031
Source
pubmed
Published In
J Clin Invest
Volume
125
Published Date
Start Page
3335
End Page
3337
DOI
10.1172/JCI83871

Survival analysis of tongue squamous cell carcinoma with CXCR4, CD44 and CD133 expression

Objective: This study aimed to analyze the correlation of the expression of CXCR4, CD44, and CD133 proteins with the clinicopathological characteristics of patients to identify the factors affecting the post-operation survival rate of tongue squamous cell carcinomas (TSCCs). Methods: Clinical data of 44 patients with TSCCs were collected and retrospectively analyzed. The diagnoses of all cases were pathologically confirmed. CXCR4, CD44, and CD133 expression in 44 TSCCs patients with different pathological grades was examined immunohistochemically. Survival curves were processed in accordance with the Kaplan-Meier method. The Cox regression model was used for the multivariate analysis of relevant clinical and survival data. Results: Among the 44 examined TSCCs patients, 29 cases were well differentiated and 15 were moderately or poor differentiated; 11 cases were stage I, 12 were stage II, 8 were stage III, and 13 were stage IV. Positive staining of CXCR4, CD44, and CD133 was found in all cases with different degrees. According to the pathological tumor grade, the positive rates of CXCR4, CD44, and CD133 expression were 79.54% (35/44 cases), 77.27% (34/44 cases), and 75.00% (33/44 cases), respectively. Expression of CXCR4, CD44, and CD133 significantly differed between different histological grades (P<0.05). Correlation analysis indicated that the expression of CXCR4, CD44, and CD133 was positively correlated with the metastasis, recurrence of TSCCs. COX multivariate analysis indicated that CXCR4 expression, clinical stage, and neck metastasis were independent prognostic predictors of TSCCs patients and risk factors of death. Conclusion: CXCR4, CD44, and CD133 may be correlated with the malignancy of TSCCs. CXCR4 expression, clinical stage, cervical lymph node metastasis were the correlated prognosis factors of TSCC patients after operation.
Authors
Nong, X; Xu, M; Li, H; Yang, Y; Nong, D; Cao, Y; Li, J; Xu, H; Li, Y
MLA Citation
Nong, X., et al. “Survival analysis of tongue squamous cell carcinoma with CXCR4, CD44 and CD133 expression.” Chinese Journal of Clinical Oncology, vol. 40, no. 14, 2013, pp. 832–37. Scival, doi:10.3969/j.issn.1000-8179.2013.14.005.
URI
https://scholars.duke.edu/individual/pub1000193
Source
scival
Published In
Chinese Journal of Clinical Oncology
Volume
40
Published Date
Start Page
832
End Page
837
DOI
10.3969/j.issn.1000-8179.2013.14.005

The role of natural regulatory T cells in infection.

Naturally occurring regulatory T cells (T(Reg)) suppress multiple cell types of the immune system to maintain dominant tolerance to protect from autoimmunity, down-modulate anti-tumor immunity and restrain allergic diseases. In addition to these functions, T(Reg) can alter effector responses to invading pathogens, leading to a variety of outcomes affecting both the host and infecting microorganisms. Here, we review how T(Reg) can influence the immune responses to chronic infections where pathogen-specific T(Reg) can contribute to pathogen persistence and, in some cases, concomitant immunity, as well as control immunopathology associated with robust immune responses. We also review the data on T(Reg) during acute infection, focusing on the questions these studies raise regarding the most appropriate model(s) to examine T(Reg) during infection. Finally, we discuss the ways in which the T(Reg) function can be altered by invading pathogens and how these can be exploited to develop methods therapeutically to influence disease and vaccine outcomes.
Authors
Sanchez, AM; Yang, Y
MLA Citation
Sanchez, Ana M., and Yiping Yang. “The role of natural regulatory T cells in infection..” Immunol Res, vol. 49, no. 1–3, Apr. 2011, pp. 124–34. Pubmed, doi:10.1007/s12026-010-8176-8.
URI
https://scholars.duke.edu/individual/pub807219
PMID
21116872
Source
pubmed
Published In
Immunol Res
Volume
49
Published Date
Start Page
124
End Page
134
DOI
10.1007/s12026-010-8176-8

Targeting the TLR9-MyD88 pathway in the regulation of adaptive immune responses.

IMPORTANCE OF THE FIELD: Toll-like receptors (TLRs) are innate immune receptors critical in the innate immune defense against invading pathogens. Recent advances also reveal a crucial role for TLRs in shaping adaptive immune responses, conferring a potential therapeutic value to their modulation in the treatment of diseases. AREAS COVERED IN THIS REVIEW: The aim of this review is to discuss TLR9, the TLR9-MyD88 signaling pathway and its role in regulation of adaptive immune responses, as well as potential therapeutic implications by targeting this pathway. WHAT THE READER WILL GAIN: This review shows that the TLR9-MyD88 signaling pathway plays a critical role in promoting adaptive immune responses and that modulation of this pathway may have enormous therapeutic potential in enhancing vaccine potency, controlling autoimmunity, as well as improving the outcome of viral-vector-mediated gene therapy. TAKE HOME MESSAGE: Although TLR9 agonists have been used as adjuvants for enhancing vaccine potency, further exploitation of the TLR9-MyD88 pathway and its dynamic interaction with the immune system in vivo is needed to provide more effective therapeutic inventions in the design of vaccines for infectious diseases, allergies and cancer, in the control of autoimmunity, as well as in the improvement of viral-vector-mediated gene therapy.
Authors
MLA Citation
Huang, Xiaopei, and Yiping Yang. “Targeting the TLR9-MyD88 pathway in the regulation of adaptive immune responses..” Expert Opin Ther Targets, vol. 14, no. 8, Aug. 2010, pp. 787–96. Pubmed, doi:10.1517/14728222.2010.501333.
URI
https://scholars.duke.edu/individual/pub777565
PMID
20560798
Source
pubmed
Published In
Expert Opin Ther Targets
Volume
14
Published Date
Start Page
787
End Page
796
DOI
10.1517/14728222.2010.501333

Research Areas:

Acute Disease
Adaptive Immunity
Adenoviridae
Adenoviridae Infections
Adenovirus E1A Proteins
Adenovirus E1B Proteins
Adenoviruses, Human
Adjuvants, Immunologic
Adoptive Transfer
Aged
Alternative Splicing
Antibody Formation
Antigen Presentation
Antigens, CD4
Antigens, CD8
Antigens, Neoplasm
Antigens, Viral
Antineoplastic Agents
Autoantigens
Autoimmune Diseases
Autoimmunity
Blotting, Western
CD4 Antigens
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Proliferation
Chaperonins
Chloride Channels
Coculture Techniques
Combined Modality Therapy
Cyclic AMP
Cystic Fibrosis Transmembrane Conductance Regulator
Cytokines
Cytotoxicity, Immunologic
DNA, Viral
Dendritic Cells
Dependovirus
Disease Models, Animal
Electric Conductivity
Endoplasmic Reticulum
Endosomes
Extracellular Signal-Regulated MAP Kinases
Female
Flow Cytometry
Gene Deletion
Gene Knock-In Techniques
Gene Transfer Techniques
Gene therapy
Genes, Bacterial
Genes, Viral
Genetic Therapy
Germinal Center
Glucose
Graft vs Host Disease
Growth Inhibitors
HLA Antigens
HLA-C Antigens
Heat-Shock Proteins
Hemagglutinins
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Heparitin Sulfate
Histocompatibility
Histocompatibility Testing
Humans
Immune System
Immune Tolerance
Immunity, Cellular
Immunity, Innate
Immunologic Memory
Immunosuppressive Agents
Immunotherapy
Influenza A virus
Interferon Type I
Interferon-beta
Interleukin-10
Interleukin-12
Interleukin-13
Interleukin-2
Interleukin-6
Killer Cells, Natural
Luciferases
Lung Neoplasms
Lymphocyte Activation
Lymphocyte Depletion
Lymphocyte Transfusion
Lymphocytes
Lymphoma
Lymphopenia
Macrophages
Male
Membrane Glycoproteins
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Knockout
Mice, Mutant Strains
Mice, Nude
Mice, Transgenic
Microsomes
Middle Aged
Mitosis
Molecular Sequence Data
Myelodysplastic Syndromes
Myeloid Cells
Myeloid Differentiation Factor 88
NK Cell Lectin-Like Receptor Subfamily K
Neoplasms
North Carolina
Oocytes
Peripheral Blood Stem Cell Transplantation
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
RNA, Messenger
Receptors, Cell Surface
Receptors, Interleukin-1
Receptors, KIR
Recombinant Proteins
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
STAT1 Transcription Factor
Sequence Deletion
Stem Cell Transplantation
Survival Rate
T-Cell Antigen Receptor Specificity
T-Lymphocytes
T-Lymphocytes, Cytotoxic
T-Lymphocytes, Regulatory
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptor 8
Toll-Like Receptor 9
Toll-Like Receptors
Transfection
Transgenes
Transplantation Conditioning
Transplantation, Homologous
Tumor Escape
Vaccines
Vaccinia
Vaccinia virus
Virus Diseases
Viruses
Xenopus
beta-Galactosidase