Search results for "Granzyme B"
showing 4 items of 14 documents
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…
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…