Archetypes of checkpoint-responsive immunity.

Archetypes of checkpoint-responsive immunity.
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DOI:
10.1016/j.it.2021.09.007
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发表时间:
2021-11
影响因子:
16.8
通讯作者:
Krummel MF
Krummel MF
中科院分区:
医学1区
文献类型:
--
作者:
Im K;Combes AJ;Spitzer MH;Satpathy AT;Krummel MF

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目前,癌症对免疫检查点阻断(ICB)治疗的反应性是通过不同的个体测量来预测的-具有不同程度的准确性-包括肿瘤突变负荷,肿瘤浸润性T细胞密度,树突状细胞频率和检查点配体的表达。我们提出,许多这些个人参数是联系在一起的,形成两个不同的“反应性”免疫原型-细胞和基因表达的集合-在ICB反应患者。我们假设这些是抗肿瘤免疫的“种子”,并由肿瘤微环境(TME)的特定元素和微生物组的作用支持。虽然去除TME中的“免疫抑制”因子很重要,但理解和解析反应性免疫对于最佳预后以及将这种生物学与候选疗法结合以提高肿瘤治愈率至关重要。
Responsiveness to immune checkpoint blockade (ICB) therapy in cancer is currently predicted by disparate individual measures – with varying degrees of accuracy – including tumor mutation burden, tumor-infiltrating T cell densities, dendritic cell frequencies, and the expression of checkpoint ligands. We propose that many of these individual parameters are linked, forming two distinct ‘reactive’ immune archetypes – collections of cells and gene expression – in ICB-responsive patients. We hypothesize that these are ‘seeds’ of antitumor immunity and are supported by specific elements of the tumor microenvironment (TME) and by actions of the microbiome. Although removing ‘immunosuppressive’ factors in the TME is important, understanding and parsing reactive immunity is crucial for optimal prognosis and for engaging this biology with candidate therapies to increase tumor cure rates.
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