tumorimmunity要点.ppt

* 肿瘤生长形成瘤细胞集团后，肿瘤抗原编码基因可能发生突变，干扰或逃避机体的免疫识别。 * This is a initial tumor clone. Because of genomic instability the initial tumor cell can proliferate to produce tumor variants. After natural selection of tumor variants the selected tumor cells proliferate to form a tumor. The green and blue tumor cells are removed. The immunotherapy or active accination or adoptive cellular transfer can kill most of tumor cells, leaving immune-refractory phenotypes survival. These tumor cells can rapidly growth and produce another new phenotypes because of genomic instability. * * Tumors secrete various factors (for example, vascular endothelial growth factor, macrophage colony-stimulating factor and interleukin(IL-6) that promote the accumulation of myeloid cells with immune-suppressive properties. These myeloid cells suppress T-cell immunity by various mechanisms, including depletion of arginine, elaboration of reactive oxygen species (ROS) and nitric oxide (NO). The tumor microenvironment also promotes the accumulation of regulatory T cells that suppress T-cell function through a host of mechanisms, some of which include secretion of IL-10 or transforming growth factor- ?. IL-10 and TGF- ? are often directly secreted by tumour cells to the same effect. Should all this fail, tumors by virtue of their genetic instability can escape immune elimination by downregulating the tumour antigens or the antigen-processing machinery. metabolism Macrophage functions in the tumor microenvironment. Immunosuppression: Tumor-associated macrophages (TAMs) dampen host immune responses against the tumor by secreting immunomodulatory cytokines and growth factors; this can occur at the primary tumor site or in distant locations where lymphocyte maturation takes place, including lymph nodes. TAM-generated molecules prevent the accumulation of anti-tumorigenic cells in the tumor (i.e. cytotoxic T cells), recruit other immune dampening cells (i.e. regulatory T cells or Tregs), and/or down-regulate require