CELL:UVB诱导的肿瘤异质性减少黑素瘤的免疫应答

2019-09-15 海北 MedSci原创

最近,研究人员在一个新的可控的小鼠黑色素瘤模型中研究这个问题,这使研究人员能够探索肿瘤内异质性(ITH)对肿瘤侵袭性和免疫力的影响,而不受肿瘤突变负荷的影响。

虽然克隆新抗原负担与免疫疗法的改善反应有关,但其功能基础仍不清楚。

最近,研究人员在一个新的可控的小鼠黑色素瘤模型中研究这个问题,这使研究人员能够探索肿瘤内异质性(ITH)对肿瘤侵袭性和免疫力的影响,而不受肿瘤突变负荷的影响。

UVB衍生突变的诱导产生具有高度侵袭性的肿瘤,其抗肿瘤活性降低。然而,具有降低的ITH的单细胞衍生的肿瘤被迅速排除。它们的排斥反应伴随着增加的T细胞反应性和较低的抑制性微环境。

利用系统发育分析和单细胞克隆的混合实验,研究人员剖析了ITH的两个特征:形成肿瘤的克隆数量及其克隆多样性。研究人员对黑素瘤患者肿瘤数据的分析概括了研究人员在总体存活率和对免疫检查点治疗的反应方面的结果。

这些研究结果突出了克隆突变在强大的免疫监视中的重要性,以及量化患者ITH以确定对检查点阻滞的反应的必要性。


原始出处:

Yochai Wolf et al. UVB-Induced Tumor Heterogeneity Diminishes Immune Response in Melanoma. Cell, 2019; DOI:https://doi.org/10.1016/j.cell.2019.08.032


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