Uveal melanoma as a target for immune-therapy
75
Citation
77
Reference
10
Related Paper
Citation Trend
Abstract:
Uveal melanoma (UM) is a rare disease that can be deadly in spite of adequate local treatment. Systemic therapy with chemotherapy is usually ineffective and new-targeted therapies have not improved results considerably. The eye creates an immunosuppressive environment in order to protect eyesight. UM cells use similar processes to escape immune surveillance. Regarding innate immunity the production of macrophage inhibiting factor (MIF) and TGF-β, added to MHC class I upregulation, inhibits the action of natural killer (NK) cells. UM cells produce cytokines such as IL-6 and IL-10 that favor macrophage differentiation to the M2 subtype, which promote tumor growth instead of an effective immune response. UM cells also impair the adaptive immune response through production of indoleamine 2,3-dioxygenase (IDO), overexpression of programmed death ligand-1 (PD-L1), alteration of FasL expression, and resistance to perforin. This biological background suggests that immunotherapy could be effective in fighting UM. A Phase II clinical trial with Ipilimumab has shown promising results with mean Overall Survival rate of ten months, and close to 50% of the patients alive at one year. Clinical trials with anti-PD1 antibodies in monotherapy and in combination with anti-CTLA4 are currently recruiting patients worldwide.Innate lymphoid cell
CCL18
Intrinsic immunity
Cite
Citations (1,771)
CD8+ T cells were previously shown to be important in preventing lymphoproliferation and immunodeficiency following infection of murine AIDS (MAIDS)-resistant mice with the LP-BM5 mixture of murine leukemia viruses. To further evaluate the mechanisms contributing to MAIDS resistance, we studied mice lacking CD8+ T cells or deficient in perforin due to knockout of the beta2-microglobulin (beta2M) or perforin gene, respectively. In contrast to wild-type, MAIDS-resistant controls, B10.A mice homozygous for the beta2M mutation and B10.D2 mice homozygous for the perforin mutation were diagnosed as having MAIDS by 5 to 8 weeks after infection by the criteria of lymphoproliferation, impaired proliferative responses to mitogens, and changes in cell populations as judged by histopathology and flow cytometry. Unexpectedly, there was no progression of lymphoproliferation through 24 weeks, even though immune functions were severely compromised. Expression of the defective virus responsible for MAIDS was enhanced in spleens of the knockouts in comparison with wild-type mice. These results demonstrate that perforin-dependent functions of CD8+ T cells contribute to MAIDS resistance but that other, non-CD8-dependent mechanisms are of equal or greater importance.
Gene knockout
Cite
Citations (19)
Immunosuppression
Adaptive response
Cite
Citations (56)
The immune system is divided into innate and adaptive immunity. Either immunity consists of humoral and cellular responses, and immunity is maximized when both responses coordinately function. Adaptive immunity has been intensively studied, while it was only recently that we gained some understanding of innate immunity. In particular, cellular responses in innate immunity have been poorly understood compared with humoral responses. In addition, the mechanisms and roles of innate immune responses could be distinct between the organisms that possess both innate and adaptive immunity and those possessing only innate immunity. On the other hand, invading pathogenic microbes employ various strategies to inhibit the host immune system for their survival. I here summarize what needs to be known to gain a deeper understanding of the innate immune response. The readers are suggested to refer to the accompanying articles for more detailed description.
Intrinsic immunity
Humoral immunity
Cellular immunity
Innate lymphoid cell
Cite
Citations (2)
Zoie immune system including innate immunity and adaptive immunity.Innate immune system is a general defense mechanism which is built up in the process of development and evolution of biological spe-cies,including tissue barrier function,cell-mediated immunity,and humor immunity.Innate immunocytes ale activated by the recognition of mode elements on the pathogen.The immunological effect is producedthronsh special signal transduction pathway:Earthworm belongs to invertebrate whose immune system lacks immunoglobulin and has not developed adaptive immunity.So earthworm protects itself tllrough innate immu-nity.
Key words:
Earthworm; Innate immunity; Nuelease
Intrinsic immunity
Innate lymphoid cell
Cite
Citations (0)
Intrinsic immunity
Innate lymphoid cell
CCL18
Cite
Citations (0)
Cite
Citations (6)
Innate lymphoid cell
Intrinsic immunity
Adaptive response
Cite
Citations (9)