Search results for "Granzyme"

Serological identification of HSP105 as a novel non-Hodgkin lymphoma therapeutic target.

2011

Abstract We reported that the clinical efficacy of dendritic cell–based vaccination is strongly associated with immunologic responses in relapsed B-cell non-Hodgkin lymphoma (B-NHL) patients. We have now investigated whether postvaccination antibodies from responders recognize novel shared NHL-restricted antigens. Immunohistochemistry and flow cytometry showed that they cross-react with allogeneic B-NHLs at significantly higher levels than their matched prevaccination samples or nonresponders' antibodies. Western blot analysis of DOHH-2 lymphoma proteome revealed a sharp band migrating at approximately 100 to 110 kDa only with postvaccine repertoires from responders. Mass spectrometry ident…

Immunological characteristics of non-intensive care hospitalized COVID-19 patients: A preliminary report

2021

The outbreak of coronavirus disease 2019 (COVID-19) is posing a threat to global health. This disease has different clinical manifestations and different outcomes. The immune response to the novel 2019 coronavirus is complex and involves both innate and adaptive immunity. In this context, cell-mediated immunity plays a vital role in effective immunity against SARS-CoV-2. Significant differences have been observed when comparing severe and non-severe patients. Since these immunological characteristics have not been fully elucidated, we aimed to use cluster analysis to investigate the immune cell patterns in patients with COVID-19 who required hospitalization but not intensive care. We identi…

Analysis of memory and effector CD8+ T cell subsets in chronic graft-versus-host disease.

2009

In humans, the selective depletion of CD8+ cells may prevent GVHD after allogeneic transplantation. These cells can infiltrate and damage target tissues. It is of interest to investigate the phenotypical characteristics and cytotoxic properties of the different CD8+ subsets in cGVHD patients. In a preliminary study we found that patients with cGVHD had a markedly elevated percentage of peripheral blood CCR7−/CD45RA+ cells compared to patients without cGVHD; conversely, the CCR7+/CD45RA+ subsets of CD8+ cells was significantly decreased. In this study, we report in depth on the phenotype of effector T cell subsets in cGVHD patients, as well as their proliferative capability, cytotoxic prope…

IL-10 Controls Ultraviolet-Induced Carcinogenesis in Mice

2007

Abstract UV radiation-induced immunosuppression contributes significantly to the development of UV-induced skin cancer by inhibiting protective immune responses. IL-10 has been shown to be a key mediator of UV-induced immunosuppression. To investigate the role of IL-10 during photocarcinogenesis, groups of IL-10+/+, IL-10+/−, and IL-10−/− mice were chronically irradiated with UV. IL-10+/+ and IL-10+/− mice developed skin cancer to similar extents, whereas IL-10−/− mice were protected against the induction of skin malignancies by UV. Because UV is able to induce regulatory T cells, which play a role in the suppression of protective immunity, UV-induced regulatory T cell function was analyzed…

Study of the immunophenotype of the inflammatory cells in melanomas with regression and halo nevi.

2015

Abstract The pathogenesis and prognostic implications of regression in melanoma are not well understood. It has traditionally been considered an immunologically mediated phenomenon. Improvement in the knowledge of the mechanisms that lead to regression may prove to be of great value in an era in which treatments oriented to the augmentation of the host's immunity against melanoma have demonstrated excellent clinical results. This study was designed to improve the understanding of the mechanisms underlying melanoma regression and the differences between similar situations in benign melanocytic nevus. The study sample consisted of 77 lesions: 62 melanomas and 15 halo nevi. The following marke…

Neuroinflammation by cytotoxic T-lymphocytes impairs retrograde axonal transport in an oligodendrocyte mutant mouse.

2012

Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow tr…

B CELL CHANGES IN AGING

2014

The aging of the immune system is a gradual and dynamic process that modifies some immunological functions. These changes are known as “immunosenescence” that have a great impact on immune performance in late life, contributing to the decreased ability of the elderly people to respond to emerging pathogens and to the decreased responsiveness to vaccinations. It is known that the adaptive immune functions are affected in the aged. In particular, with aging, the acquired compartment of the immune system shows significant modifications in both T and B cell branches. Thus, the adaptive immune response of elderly people is qualitatively and quantitatively reduced when compared to that observed i…

Granzyme A is an additional marker for tuberculosis (TB) to discriminate between patients with active disease and subjects with latent infection.

2013

Study of mechanisms of action of an immunotherapy by triacyl lipid A in humans

2013

Immunotherapy acting at the primary tumor site and preventing the development of metastases is one of the strategies for treatment of patients with cancer. To improve the efficiency of the latter, it is necessary to understand how it induces tumor cell death. In the laboratory, it was observed the cure of PROb tumors in rats BDIX by the triacyl lipid A. It has been shown that this effect involved the immune system involving interactions with TLRs present in many tumor cells and innate immunity cells such as neutrophils.In this work, we investigated the possible involvement of neutrophils in the antitumor activity of triacyl lipid A in humans.In a Phase 1 study in patients with refractory so…

Etude des mécanismes d'action d'une immunothérapie par un lipide A, seul ou associé à l'oxaliplatine, dans des modèles de cancers coliques

2013

Colorectal cancer is a major public health concern in France. Resistance to standard chemotherapy requires development of novel therapeutic approaches. In the past decades, our team showed the immunotherapeutic properties of lipid A in a model of colon cancer in rats. 95% of rats bearing small carcinomas were cured following treatment by lipid A. The study of mechanisms underlying this immunotherapy allowed us to show that the antitumor effect of lipid A was dependent on cytotoxicity induced by granzyme B produced by intratumoral neutrophils. Indeed, we have shown that, in the tumor microenvironment, neutrophils produced granzyme B and had a pro-tumorigenic N2 phenotype. When rats were trea…