Lymphoid chemockine secretion by B16 melanoma cancer cells and it effects on communication with lymphatics and the immune systhem
Tutor / director / avaluadorSwartz, Melody
Tipus de documentProjecte/Treball Final de Carrera
Condicions d'accésAccés restringit per acord de confidencialitat
Expression of CCR7 receptor on tumor cells membrane correlates with lymph node metastases in many human cancers and evidence suggests that tumor cells which also secrete CCR7-ligands can drive their own chemotaxis towards lymphatic guided by fluid flow from the tumor to draining lymphatic. Autocrine signals and paracrine signals from lymphatic endothelial cells both guide tumor cells chemotaxis and relative contributions were modeled computationally by Shields and Fleury for a single tumor cell. This model was further developed to assess how a growing tumor could detect autocrine vs paracrine signal and predicted that when the tumor mass gets bigger paracrine signal loses relevance. To verify this experimentally, we developed a physiologically relevant assay to quantify migration of different tumor cell densities and to show that indeed the lymphatic endothelial signal becomes of less importance when cell density increases. In the second part of our study we consider the role of the enzyme Indoleamine 2,3 dioxygenase (IDO) as one molecular mechanism that contributes to tumor induced tolerance. There have been many reported mechanisms explaining that, by attracting immune cells, a tumor can control the immune response. From all the immunosuppressive networks taking place, we have chosen to explore the role of IDO+ DCs in the tumor environment.
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