Influence of TNF and TGF-beta on Langerhans cell mobilisation from regressor and progressor skin tumours

皮肤癌是人类最常见的癌症类型。它是由阳光中的紫外线波长引起的。澳大利亚的皮肤癌发病率是世界上最高的，这是因为澳大利亚人在工作和休闲时经历了大量的阳光暴晒。需要对这种疾病进行大量研究，以了解它是如何形成的，以及如何治疗。皮肤癌可以由免疫系统控制，在某些情况下，免疫系统能够摧毁癌症，使其消失或退化。其他皮肤肿瘤不能被免疫系统摧毁，因此会逐渐生长。进展型和退化型肿瘤之间的差异可以帮助确定为什么免疫系统能够摧毁一些肿瘤，而不是其他肿瘤。负责启动对皮肤癌的免疫反应的免疫系统细胞被称为朗格汉斯细胞。这种细胞在癌症和局部淋巴结之间迁移，在那里它激活淋巴细胞离开淋巴结并摧毁癌症。我们的研究表明，进展型和退化型皮肤肿瘤之间的一个主要区别是郎格汉斯细胞从这些肿瘤中迁移的能力。皮肤肿瘤产生细胞因子(激素样分子)，促进或抑制郎格汉斯细胞从肿瘤中动员。我们已经确定了一些涉及的细胞因子，并计划研究这些细胞因子如何干扰这一过程，以及它们是通过增加其他因子的产生来实现这一点，还是通过直接影响朗格汉斯细胞来实现这一点。这一知识将提高我们利用这些细胞治疗癌症的能力。这项研究还将进一步了解调节这种重要细胞从我们的组织移动到引流淋巴结的生物学因素，这对免疫的发展至关重要。

Skin cancer is the most common type of cancer in humans. It is caused by the ultraviolet wavelengths found in sunlight. Australia has the highest incidence of skin cancer in the world, due to the large amount of sun exposure experienced by Australians during work and leisure. Considerable research needs to be directed towards this disease to understand how it forms and how it can be treated. Skin cancer can be controlled by the immune system, which in some cases is able to destroy the cancer, so that it disappears, or regresses. Other skin tumours fail to be destroyed by the immune system and therefore grow progressively. Differences between progressor and regressor tumours can help define why the immune system is able to destroy some but not other tumours. The cell of the immune system that is responsible for initiating immune responses against skin cancer is called the Langerhans cell. This cell migrates between the cancer and the local lymph node, where it activates lymphocytes to leave the lymph node and destroy the cancer. Our studies have shown that a major difference between progressor and regressor skin tumours is the ability of Langerhans cells to migrate from these tumours. Skin tumours produce cytokines (hormone like molecules) which enhance or inhibit Langerhans cell mobilization from the tumour. We have identified some of the cytokines involved, and plan to study how these cytokines interfere with this process and whether they do this by increasing the production of other factors, or by having a direct influence on the Langerhans cells. This knowledge would increase our ability to utilize these cells for treatment of cancer. This study will also further basic understanding of the biological factors which regulate the movement of this important cell from our tissues to the draining lymph node, which is of fundamental importance in the development of immunity.