<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Dynamic intravital imaging reveals a T lymphocyte\r\nrecruitment mechanism to melanoma brain tumors"^^ . "Cutaneous malignant melanoma is a rare, but very aggressive type of skin cancer, that frequently\r\nmetastasizes to the brain. As treatment options for patients suffering from brain metastases are very\r\nlimited, the diagnosis of brain metastasis is associated with a poor prognosis. However, recent\r\npreclinical and clinical findings raise hope that immunotherapeutic approaches could benefit brain\r\nmetastasis patients. Intracranial anti‐tumor response to immune checkpoint inhibition (ICI) is possible\r\nbut strongly depends on efficient T cell recruitment to the brain. While the brain has long been\r\nconsidered an immune privileged organ, recent studies have suggested that special meningeal\r\nlymphatic vessels facilitate immune surveillance of brain tissue. However, in the context of brain\r\ntumors, the mechanism of T cell recruitment to the brain, and how this is affected by ICI, is still poorly\r\nunderstood. To elucidate anatomical and molecular mechanisms of T cell homing to brain tumors, I\r\nestablished novel intravital microscopy methods that allow to track T cell and tumor cell interactions\r\nin real‐time over two weeks in two different syngeneic mouse models for melanoma brain tumors.\r\nWith this, I was able to visualize the dynamics of T cell recruitment to the brain during tumor\r\ndevelopment, and I discovered a new route for circulating T cells to access brain tumors via distinct\r\nanatomical structures, namely peritumoral venous vessels (PVVs). Exploitation of PVVs for T cell\r\nhoming to intracranial tumors was enhanced by ICI treatment. I could demonstrate that PVVs are the\r\nsites where circulating T cells preferably arrest and extravasate. Other structures, such as brain\r\ncapillaries, intratumoral blood vessels, and parasagittal regions could be excluded as alternative T cell\r\nroutes to intracranial melanoma. Moreover, at PVVs, a particularly high T cell motility and number was\r\nobserved, and PPVs were characterized by high luminal expression of the endothelial intercellular\r\nadhesion molecule 1 (ICAM‐1). Indeed, a trend of mitigation of ICI‐mediated T cell infiltration and\r\nintracranial tumor growth control could be detected following functional blocking of ICAM‐1 in vivo.\r\nICI treatment increased T cell motility in the brain, facilitating the route from the PVV to the tumor,\r\nwhich resulted in intracranial tumor growth inhibition. These findings describe a distinct mechanism\r\nby which cellular components of the adaptive immune system can access and control brain tumors,\r\nand potentially other brain pathologies. The molecular and cellular features of PVVs, and also the\r\nspecific effects of ICIs on T cell functionality in the brain in vivo, which is described for the first time,\r\nprovide a fundament which will help to further improve immunotherapies against brain tumors."^^ . "2022" . . . . . . . "Julia Maria"^^ . "Meßmer"^^ . "Julia Maria Meßmer"^^ . . . . . . "Dynamic intravital imaging reveals a T lymphocyte\r\nrecruitment mechanism to melanoma brain tumors (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Dynamic intravital imaging reveals a T lymphocyte\r\nrecruitment mechanism to melanoma brain tumors (PDF)"^^ . . . "PhDThesis_JuliaMessmer.pdf"^^ . . . "Dynamic intravital imaging reveals a T lymphocyte\r\nrecruitment mechanism to melanoma brain tumors (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Dynamic intravital imaging reveals a T lymphocyte\r\nrecruitment mechanism to melanoma brain tumors (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Dynamic intravital imaging reveals a T lymphocyte\r\nrecruitment mechanism to melanoma brain tumors (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Dynamic intravital imaging reveals a T lymphocyte\r\nrecruitment mechanism to melanoma brain tumors (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #32202 \n\nDynamic intravital imaging reveals a T lymphocyte \nrecruitment mechanism to melanoma brain tumors\n\n" . "text/html" . .