Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma.
Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma.
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DOI：
10.1016/j.celrep.2022.110639
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发表时间：
2022-04-05
期刊：
影响因子：
8.8
通讯作者：
McGraw, Timothy E.
中科院分区：
文献类型：
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作者：
Altorki, Nasser K.;Borczuk, Alain C.;Harrison, Sebron;Groner, Lauren K.;Bhinder, Bhavneet;Mittal, Vivek;Elemento, Olivier;McGraw, Timothy E.
为了研究肺癌进展过程中肿瘤微环境（TME）的变化，我们询问了来自两个胸部计算机断层扫描（CT）定义的组的肿瘤。纯非实性 (pNS) CT 密度结节包含浸润前/微创癌症，实性密度结节包含浸润性癌症。分析数据揭示了肿瘤及其 TME 在整个进展过程中的动态相互作用。调节细胞外基质的基因和调节成纤维细胞的基因的改变是侵袭前状态的中心。 T 细胞介导的免疫抑制在浸润前结节中启动，并随着进展为浸润性肿瘤而持续增强。癌细胞巢中 T 细胞浸润的减少更常与浸润前癌症相关，可能直到肿瘤进化导致持久、可行的侵袭表型，并伴有更多样化和更强大的免疫抑制。免疫检查点的上调仅发生在侵袭性结节中。在整个进展过程中，存在效应免疫反应，但会受到免疫抑制因素的有效阻碍。 CT 扫描识别的肺结节提出了重大的临床挑战。阿尔托基等人。定义特征，包括免疫背景和微环境特征，区分正常肺、浸润前和浸润性结节。通过捕捉疾病进展的早期特征，他们为未来的拦截策略提供信息，并确定机制研究中需要研究的关键问题。
To investigate changes in the tumor microenvironment (TME) during lung cancer progression, we interrogate tumors from two chest computed tomography (CT)-defined groups. Pure non-solid (pNS) CT density nodules contain preinvasive/minimally invasive cancers, and solid density nodules contain invasive cancers. Profiling data reveal a dynamic interaction between the tumor and its TME throughout progression. Alterations in genes regulating the extracellular matrix and genes regulating fibroblasts are central at the preinvasive state. T cell-mediated immune suppression is initiated in preinvasive nodules and sustained with rising intensity through progression to invasive tumors. Reduced T cell infiltration of the cancer cell nests is more frequently associated with preinvasive cancers, possibly until tumor evolution leads to a durable, viable invasive phenotype accompanied by more varied and robust immune suppression. Upregulation of immune checkpoints occurs only in the invasive nodules. Throughout progression, an effector immune response is present but is effectively thwarted by the immune-suppressive elements. CT-scan-identified lung nodules present a significant clinical challenge. Altorki et al. define characteristics, both immune-context and microenvironment features, distinguishing normal lung, preinvasive, and invasive nodules. By capturing early features of disease progression, they inform future interception strategies and identify key questions to be investigated in mechanistic studies.
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