Search results for " Immunological"
showing 10 items of 87 documents
Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study
2018
Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age 35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks tra…
French Endocrine Society Guidance on endocrine side effects of immunotherapy.
2018
The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing…
A potential role of interferon-gamma in the pathogenesis of venous leg ulcers.
2005
Venous leg ulcer is the most severe expression of chronic venous insufficiency. Venous ulcerations are always associated with venous ambulatory hypertension, but the exact mechanism leading from pathological hemodynamics in venous circulation to the necrotic lesions in the skin still remains undiscovered. It has been shown that tissue injury in venous ulcer patients was induced by leukocytes. However, though infiltrating leukocytes have at their disposal a powerfully cytotoxic arsenal, it has not been discovered which molecular mechanisms may contribute to the skin damage. The search for this hypothetical factor responsible for the development of ulceration should be focused on mechanisms l…
Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions
2016
Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFNγ secretion by CD8+ T cells is critical for therapy efficacy having anti-proliferative and pro-apoptotic effects on tumour cells. Our study demonstrates a genetic evolution of IFNγ resistance in different melanoma patient models. Chromosomal alterations and subsequent inactivating mutations in genes of the IFNγ signalling cascade, most often JAK1 or JAK2, protect melanoma cells from anti-tumour IFNγ activity. JAK1/2 mutants further evolve into T-cell-resistant HLA class I-negative lesions with genes involved in antigen presentation silenced and no longer inducible by IFNγ. Allelic JAK1/2 losses predisposing to …
Epithelial-mesenchymal communication in the pathogenesis of chronic asthma.
2005
Although Th-2-mediated inflammation is a key therapeutic target in asthma, its relationship to altered structure and functions of the airways is largely unknown. In addition to inflammation, asthma is a disorder involving the airway epithelium that is more vulnerable to environmental injury and responds to this by impaired healing. This establishes a chronic wound scenario that is capable of sustaining chronic inflammation as well as remodeling. This response occurs as a consequence of activation of the epithelial-mesenchymal unit, involving reciprocal activities of growth factors belonging to the fibroblast growth factor, epidermal growth factor, and transforming growth factor-beta familie…
Cancer and the microbiome : potential applications as new tumor biomarker
2015
Abstract: Microbial communities that colonize in humans are collectively described as microbiome. According to conservative estimates, about 15% of all types of neoplasms are related to different infective agents. However, current knowledge is not sufficient to explain how the microbiome contributes to the growth and development of cancers. Large and thorough studies involving colonized, diverse and complex microbiome entities are required to identify microbiome as a potential cancer marker and to understand how the immune system is involved in response to pathogens. This article reviews the existing evidence supporting the enigmatic association of transformed microbiome with the developmen…
Risk of scleroderma according to the type of immune checkpoint inhibitors
2020
Abstract Introduction Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). Among them, ICIs-induced systemic sclerosis (SSc) is poorly known. Methods To better characterize this irAE, our comprehensive approach combined the description of ICIs-induced scleroderma cases, the systematic review of the literature and the analysis of VigiBase, the WHO pharmacovigilance database. Results We identified two cases with underlying limited cutaneous SSc who presented a dramatic increase in the skin thickening following pembrolizumab, associated with scleroderma renal crisis in one case. In the literature, four cases of scleroderma and four cases of morphea hav…
An adaptive multimeme algorithm for designing HIV multidrug therapies.
2007
This paper proposes a period representation for modeling the multidrug HIV therapies and an Adaptive Multimeme Algorithm (AMmA) for designing the optimal therapy. The period representation offers benefits in terms of flexibility and reduction in dimensionality compared to the binary representation. The AMmA is a memetic algorithm which employs a list of three local searchers adaptively activated by an evolutionary framework. These local searchers, having different features according to the exploration logic and the pivot rule, have the role of exploring the decision space from different and complementary perspectives and, thus, assisting the standard evolutionary operators in the optimizati…
Side effect management during immune checkpoint blockade using CTLA-4 and PD-1 antibodies for metastatic melanoma – an update
2020
CTLA-4 and PD-1 play a key role in tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti-CTLA-4 and anti-PD-1 antibodies affect the interaction between tumor, antigen-presenting cells and T lymphocytes. Clinical studies of the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five-year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with …
Dendritic cell-based immunotherapy of malignant melanoma: success and limitations.
2007
Dendritic cells (DC) are professional antigen-presenting cells in the immune system which are able to induce primary T-cell responses. Because of their central role in the initiation of immune responses, DC are an important tool for tumor-antigen-specific immunotherapy of cancer. DC vaccination using tumor-antigen-loaded DC has led to tumor regression in individual advanced-stage cancer patients. However, there is a discrepancy between strong and antigen-specific T cell responses in vaccinated cancer patients detectable ex vivo and only weak clinical responses. In most cases the immune system of advanced stage IV cancer patients allows only a temporary anti-tumor response and increasing evi…