Effect of ultraviolet radiation on development of effector and memory T cells to melanoma

澳大利亚是世界上皮肤癌发病率最高的国家，这是由于我们的生活方式涉及高水平的阳光照射。包括黑色素瘤在内的皮肤癌可以被免疫系统摧毁，但阳光会抑制免疫力，使皮肤肿瘤生长。我们的目标是确定阳光如何影响效应抗黑色素瘤T细胞的激活，以及它们发育成记忆T细胞，以及产生这种效应所需的阳光剂量。目前尚不清楚阳光中的紫外线辐射是否会抑制介导皮肤肿瘤排斥反应的效应细胞的活化，或抑制其发育为记忆细胞，或抑制活化的记忆淋巴细胞迁移到皮肤肿瘤中。抗原反应性T细胞的数量是肿瘤免疫的关键问题，许多临床免疫治疗试验的目的是将这些细胞提高到可以有效摧毁肿瘤的水平。重要的是要确定在正常生活中容易获得的低剂量阳光，或仅在日光照射时接受较高的暴露，是否会抑制这些效应T细胞的数量及其迁移到皮肤肿瘤中。重要的是要确定是否有一个相对安全的阳光照射阈值水平，以便能够提供更好的建议，可以达到阳光剂量，而不会造成严重的有害健康影响。此外，这些阳光水平可能会干扰免疫治疗试验，因此需要确定。另一个结果将是确定是否化学预防剂，提高从阳光诱导的抑制皮肤过敏的恢复也保护抗肿瘤免疫。建立预防抗肿瘤免疫抑制的程序可以增加由天然免疫或免疫治疗期间激活的T细胞的数量，从而改善黑色素瘤的免疫排斥。

Australia has the highest incidence of skin cancer in the world, due to our lifestyle that involves high levels of exposure to sunlight. Skin cancer, including melanoma can be destroyed by the immune system, but sunlight inhibits immunity, enabling skin tumours to grow. Our aim is to determine how sunlight affects the activation of effector anti-melanoma T cells, and their development into memory T cells, and the dose of sunlight required to have this effect. It is unknown whether ultraviolet radiation in sunlight suppresses the activation of effector cells that mediate rejection of skin tumours, or their development into memory cells, or migration of activated-memory lymphocytes into skin tumours. The number of antigen reactive T cells is a key issue for tumour immunity and the aim of many clinical immunotherapy trials is to boost these to levels that can effectively destroy the tumour. It is important to establish whether low doses of sunlight readily achievable during normal living, or only higher exposures received when sunbaking, inhibit the number of these effector T cells, and their migration into skin tumours. It is important to determine whether there is a relatively safe threshold level of sunlight exposure to be able to give better advice on sunlight doses that can be achieved without causing serious deleterious health effects. Also these levels of sunlight may interfere with immunotherapy trials and therefore need to be determined. An additional outcome will be to determine whether chemopreventative agents that enhance recovery from sunlight induced suppression of skin allergies are also protective for anti-tumour immunity. The establishment of procedures for prevention of suppression of anti-tumour immunity may enhance the number of T cells activated by natural immunity or during immunotherapy, thereby improving immune rejection of melanoma.