Host Defence Against Cancer

There is no doubt that the immune system can recognise and eliminate malignant tumour cells in vivo, even though the immunosurveillance against tumour clones has likely not been the main purpose that drove the evolution of the immune system. Consequently, it is believed that tumours, which emerge in cancer patients, have been previously selected to escape immune elimination. There is compelling evidence that both natural and adaptive immune responses are involved in tumour clearance. In particular, as far as natural immunity is concerned, it is known that nude athymic mice have comparable rates of cancer incidence relative to normal mice, this fact being mostly due to their maintained NK activity [15]. In contrast, knockout mice lacking the gene for perforin [16], IFN-y [ 17] or IFNR-y [18] have been shown to have a higher incidence of carcinogen-induced tumours and in some cases spontaneous carcinomas. From a clinical perspective, since the end of the XIX century, experimental observations on cancer patients indicated that spontaneous remission was often accompanied by an inflammatory response against a concomitant bacterial infection [19]. On the whole, both historical clinical experience and modern experimental data converge in indicating an important role for natural immunity in cancer clearance. In this regard, it has long been recognised that NK cells spontaneously kill MHC-deficient tumour cells in vivo [20], More recently, it has been observed that cancer cells can be recognised by NK, NKT, CD8+ T cells and y5 T cells through the binding of stress-induced molecules that structurally resemble MHC class I molecules. These molecules are called MICA, MICB and the ULBP family, the ortholog of the murine RAE-1 family [21,22], These molecules are normally expressed on gut epithelium and can be induced by viral infection or other stress, such as heat shock, and bind to the NKG2D receptor expressed on the surface of NK, NKT, CD8+ T cells and y8 TCR cells [23], This receptor is associated with DAP 10, a transmembrane-anchored adapter protein that can activate the PI3-kinase pathway [24], and thus is able to trigger cell-mediated cytotoxicity [23],

Dendritic cells (DC), the major antigen presenting cells, play an important role in immuno-surveillance against cancer. These cells have to be activated in order to induce fully effective T cell immunity. There is a series of studies indicating that DC, when appropriately activated and induced to present tumour-derived peptides, can very effectively elicit tumour-specific T cell immunity [25], Tumour associated antigens (TAA), such as MAGE1 and MARTI melanoma antigens, can be captured by immature DC which in turn can mature and migrate to the draining lymph node, where they can stimulate both specific CD8+ and CD4+ T cells upon expression of costimulatory molecules such as CD28 and CD40 [26], Activated CD8+ CTL and T helper CD4+ cells can then migrate into tissues and mount an attack against the developing melanoma. Based on this, different clinical trials on vaccines against melanoma are now underway. Unfortunately, most of the tumours are not targeted by the immune system for a series of rational reasons (among others, lack of specific TAAs or adequate co-stimulation, or the production of inhibitory cytokines). One of these handicaps can be overridden by inducing a localised inflammatory reaction. The production of Thl cytokines can in fact activate and orientate macrophages and T cells not only against the inflammatory agents, but also against tumour cells. This is the rationale for the most effective immune therapy that has been established up to now, i.e., Coley's toxin ( a toxin from S. pyogenes, that was used for over 40 years by William Coley in the first half of the past century, with a cure rate of 10% in inoperable sarcomas [19]), and the Bacillus Calmette-Guérin (BCG), used not only to vaccinate against TBC, but also against superficial bladder cancer [27], At present, local generation of an immune milieu by agents of the imidazoquinoline family leading to a Thl-dominance and cell-mediated immunity has been used clinically to treat viral infections such as human papillomavirus (HPV), herpes simplex virus (HSV), and cancerous lesions including initial squamous cell and basal cell carcinoma in immunocompetent and immunosuppressed patients [28],

How To Prevent Skin Cancer

How To Prevent Skin Cancer

Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.

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