Begell House Inc.
Critical Reviews™ in Immunology
CRI
1040-8401
38
3
2018
Avelumab: A Novel Anti-PD-L1 Agent in the Treatment of Merkel Cell Carcinoma and Urothelial Cell Carcinoma
159-206
10.1615/CritRevImmunol.2018025204
Amanda
Teets
School of Pharmacy, Lake Erie College of Osteopathic Medicine, Bradenton, Florida
Linda
Pham
School of Pharmacy, Lake Erie College of Osteopathic Medicine, Bradenton, Florida
Emma Lan
Tran
School of Pharmacy, Lake Erie College of Osteopathic Medicine, Bradenton, Florida
Lana
Hochmuth
School of Pharmacy, Lake Erie College of Osteopathic Medicine, Bradenton, Florida
Rahul
Deshmukh
School of Pharmacy, Lake Erie College of Osteopathic Medicine, Bradenton, Florida
avelumab
PD-L1
checkpoint inhibitors
Merkel cell carcinoma
urothelial cell carcinoma
Long-term treatment in the setting of metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma
(UC) has shown that current first-line chemotherapeutic agents are losing effectiveness and that there are limited
treatment options available outside of radiation therapy and surgical interventions. The use of immunotherapeutic
agents such as monoclonal antibodies has been considered a promising alternative for cancers that progress despite
treatment with radiation therapy, surgery, and/or chemotherapeutic agents. Cancer cells escape immune surveillance by interrupting immune checkpoint pathways, resulting in dysregulation of T-cell function and so preventing its antitumor effects. In early 2017, avelumab (BAVENCIO®), a PD-L1–blocking monoclonal antibody agent, was approved for the treatment of metastatic MCC and UC. Trials that evaluated avelumab for the treatment of metastatic MCC and UC were the JAVELIN Merkel 200 Trial and the JAVELIN Solid Tumor trial, respectively. Efficacy results for both trials showed positive overall response rate (ORR) and progression-free survival rate (PFS). A strong safety profile was also established for avelumab. This review provides a brief introduction to checkpoint inhibitors and focuses on the recently approved PD-L1 inhibitor, avelumab.
Cellular Components and Mechanisms of Oral Tolerance Induction
207-231
10.1615/CritRevImmunol.2018026181
Rafael M.
Rezende
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston,
Massachusetts
Howard L.
Weiner
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston,
Massachusetts
Oral tolerance
gut mucosa
innate and adaptive immune cells
Oral tolerance can be defined as an inhibition of specific immune responsiveness to subsequent parenteral
injections of proteins to which an individual or animal has been previously exposed via the oral route. Multiple
mechanisms of tolerance are induced by oral-fed antigens, but induction of regulatory CD4 T-cells expressing the
transcription factor Foxp3 and the membrane-bound TGF-β stands out as the major players in oral tolerance. Oral
antigen administration suppresses several animal models of autoimmune disease, including experimental autoimmune
encephalomyelitis, uveitis, thyroiditis, myasthenia, arthritis, and diabetes, but also nonautoimmune inflammatory
conditions such as asthma, atherosclerosis, graft rejection, allergy, and stroke. However, human trials have produced mixed results, and a great deal remains to be learned about the mechanisms of oral tolerance before it can be successfully applied to people. In this review, we highlight the cellular components involved in oral tolerance
induction. A deep knowledge of these intricate cell interactions will pave the way for a successful application of antigen tolerance to treat autoimmune and nonautoimmune inflammatory diseases.
Connection between γδ T-cell– and Adenosine- Mediated Immune Regulation in the Pathogenesis of Experimental Autoimmune Uveitis
233-243
10.1615/CritRevImmunol.2018026150
Dongchun
Liang
Doheny Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles,
California
Hui
Shao
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky
Willi K.
Born
Department of Biomedical Research, National Jewish Health, Denver, Colorado
Rebecca L.
O'Brien
Department of Biomedical Research, National Jewish Health, Denver, Colorado
Henry J.
Kaplan
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville,
Louisville, Kentucky
Deming
Sun
Doheny Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles,
California
adenosine deaminase (ADA)
autoimmunity
adenosine receptors
experimental autoimmune uveitis
Foxp3
gamma;delta; T-cell
regulatory T-cell
Th17
uveitis
Regulatory effects of γδ T-cells on immune responses have been studied for years. We have investigated the regulatory effect of γδ T-cells on Th1 and Th17 autoimmune responses, and have studied molecular and cellular mechanisms by which γδ T-cells enhance or inhibit immune responses, exploiting a well-characterized murine model
of experimental autoimmune uveitis (EAU). Our results show that (1) aberrant γδ T-cell activation is an important pathogenic event in EAU; (2) γδ T-cells have a unique regulatory effect on Th17 autoimmune responses, which is shaped by the activation status of γδ T-cells; and (3) γδ-mediated immunoregulation is closely linked with the extracellular adenosine metabolism. Reciprocal interactions between γδ T-cells and extracellular adenosine partially determine the development of EAU.
Roles of Steroid Receptor Coactivator 3 in Host Defense Against Bacterial Pathogens
245-252
10.1615/CritRevImmunol.2018026300
Wenbo
Chen
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China; The First Affiliated Hospital of Xiamen University, Xiamen, China
Pingli
Mo
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China
Chundong
Yu
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China
steroid receptor coactivator-3
host defense
bacterial infection
bacterial clearance
Steroid receptor coactivator 3 (SRC-3) is a transcriptional coactivator that interacts with nuclear receptors such as the estrogen receptor and the androgen receptor and several other transcription factors to enhance their effects on target gene expression. SRC-3 plays important roles in many developmental, physiological, and pathologic events, including body growth, mammary gland development, energy homeostasis, inflammatory regulation, and cancer initiation and progression. SRC-3 has been suggested to be involved in host defense against bacterial
pathogens. In this review, we summarize the roles of SRC-3 in host defense against peritoneal and enteric bacterial
infection and discuss the potential clinical implications.