ABSTRACT
Chemotherapy-induced peripheral neuropathy (CIPN) is a major comorbidity of cancer. Multiple clinical interventions have been studied to effectively treat CIPN, but the results have been disappointing, with no or little efficacy. Hence, understanding the pathophysiology of CIPN is critical to improving the quality of life and clinical outcomes of cancer patients. Although various mechanisms of CIPN have been described in neuropathic anti-cancer agents, the neuroinflammatory process involving cytotoxic/proinflammatory immune cells remains underexamined. While mast cells (MCs) and natural killer (NK) cells are the key innate immune compartments implicated in the pathogenesis of peripheral neuropathy, their role in CIPN has remained under-appreciated. Moreover, the biology of proinflammatory cytokines associated with MCs and NK cells in CIPN is particularly under-evaluated. In this review, we will focus on the interactions between MCs, NK cells, and neuronal structure and their communications via proinflammatory cytokines, including TNFα, IL-1ß, and IL-6, in peripheral neuropathy in association with tumor immunology. This review will help lay the foundation to investigate MCs, NK cells, and cytokines to advance future therapeutic strategies for CIPN.
Subject(s)
Mast Cells , Peripheral Nervous System Diseases , Humans , Quality of Life , Killer Cells, Natural , Neurons , Peripheral Nervous System Diseases/chemically induced , CytokinesSubject(s)
Mastocytosis, Systemic/drug therapy , Mastocytosis, Systemic/genetics , Molecular Targeted Therapy , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Antineoplastic Agents/therapeutic use , Clone Cells , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Dioxygenases , Female , Humans , Middle Aged , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-kit/genetics , Repressor Proteins/geneticsSubject(s)
Granulocyte Precursor Cells , Leukemia, Myeloid, Acute , Aniline Compounds , Humans , PyrazinesABSTRACT
Umbilical cord blood transplantation (UCBT) has been an important donor source for allogeneic hematopoietic stem cell transplantation, especially for patients who lack suitable matched donors. UCBT provides unique practical advantages, such as lower risks of graft-versus-host-disease (GVHD), permissive HLA mismatch, and ease of procurement. However, there are clinical challenges in UCBT, including high infection rates and treatment-related mortality in selected patient groups. These clinical advantages and challenges are tightly linked with cell-type specific immune reconstitution (IR). Here, we will review IR, focusing on T and NK cells, and the impact of IR on clinical outcomes. Better understanding of the immune biology in UCBT will allow us to further advance this field with improved clinical practice.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cytotoxicity, Immunologic/drug effects , Immunomodulation/drug effects , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Leukemia, Myeloid, Acute/immunology , Protein Kinase Inhibitors/pharmacology , Pyridinium Compounds/pharmacology , Animals , Biomarkers , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Cell Line, Tumor , Cyclic N-Oxides , Disease Models, Animal , Humans , Immunophenotyping , Indolizines , Killer Cells, Natural/metabolism , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Mice , Protein Kinase Inhibitors/therapeutic use , Pyridinium Compounds/therapeutic use , Xenograft Model Antitumor AssaysSubject(s)
Blood Cells/pathology , Leukemia, Prolymphocytic, B-Cell/drug therapy , Leukemia, Prolymphocytic, B-Cell/pathology , Pentostatin/therapeutic use , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Blood Cells/drug effects , Cell Death/drug effects , Hematologic Tests , Humans , Leukemia, Prolymphocytic, B-Cell/blood , MaleABSTRACT
OBJECTIVE: To determine the association between a history of asthma and a diagnosis of selective IgA deficiency (sIgAD)/common variable immunodeficiency (CVID). PATIENTS AND METHODS: This population-based case-control study included residents of Olmsted County, Minnesota, who met the Pan-American Group for Immunodeficiency/European Society for Immunodeficiencies diagnostic criteria for sIgAD/CVID between January 1, 1964, through December 31, 2008. Each case had 4 age- and sex-matched controls (2 from the community and 2 from a list of individuals who had undergone an immune work-up). We ascertained asthma status by applying predetermined criteria for asthma. RESULTS: We identified 39 cases: 26 (66.7%) had sIgAD and 13 (33.3%) had CVID. Of the 39 cases, 51.3% were men (n=20) and 97.1% were white (33 of 34 patients). The mean age at the index date (the time when criteria were met) of sIgAD/CVID was 34.2 years. Of the 39 cases, 9 (23.1%) had a history of asthma before the index date of sIgAD/CVID; of the 156 controls, 16 (10.3%) had a history of asthma before the index date (odds ratio, 2.77; 95% CI, 1.09-7.06; P=.03). A history of asthma (before or after the index date of sIgAD/CVID) was more prevalent in sIgAD/CVID cases (30.8%; n=12) than in matched controls (11.5%; n=18) (odds ratio, 3.57; 95% CI, 1.50-8.51; P=.01). CONCLUSION: Asthmatic patients are more likely to have a diagnosis of sIgAD/CVID than nonasthmatic individuals. This association may potentially account for the increased risks of bacterial infections in some individuals with asthma.
Subject(s)
Asthma , Common Variable Immunodeficiency , IgA Deficiency , Adult , Asthma/complications , Asthma/diagnosis , Asthma/epidemiology , Asthma/immunology , Asthma/physiopathology , Case-Control Studies , Common Variable Immunodeficiency/diagnosis , Common Variable Immunodeficiency/epidemiology , Common Variable Immunodeficiency/etiology , Female , Humans , IgA Deficiency/diagnosis , IgA Deficiency/epidemiology , IgA Deficiency/etiology , Incidence , Male , Minnesota/epidemiology , Monitoring, Immunologic , Research Design , Risk Assessment , Risk FactorsABSTRACT
Superior vena cava (SVC) syndrome is an uncommon complication of malignant disease caused by the obstruction of venous blood flow in the SVC. When present, a diagnosis of lung cancer or lymphoma will be made in approximately 95% of cases. Although other malignant diseases are occasionally associated with SVC, its occurrence in patients with prostate cancer is rare. We present a case of a patient presenting with SVC obstruction who was subsequently diagnosed with prostate adenocarcinoma. The patient has been successfully treated with GnRH agonist. This case reflects the importance of a full clinical assessment and pathological confirmation of suspected tumour prior to treatment.
