Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy.
Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy.
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DOI：
10.1136/jitc-2021-003032
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发表时间：
2021-09
影响因子：
10.9
通讯作者：
Fennell D
中科院分区：
文献类型：
--
作者：
Harber J;Kamata T;Pritchard C;Fennell D
恶性胸膜间皮瘤（MPM）是一种无法治愈的癌症，预后不佳，几乎没有有效的治疗选择。尽管如此，最近免疫检查点阻断（ICB）治疗MPM的III期试验结果为推进这种癌症的有效治疗带来了新的曙光。肿瘤突变负荷（Tumor mutation burden， TMB）已被广泛报道用于预测其他癌症的ICB，但MPM被认为是一种低TMB肿瘤。同样，肿瘤程序性死亡配体1 （PD-L1）表达在MPM的III期临床试验中也未被证明具有预测作用。因此，确定这种癌症对免疫治疗反应的确切机制仍然未知。因此，本综述旨在综合我们目前对MPM中肿瘤免疫微环境的理解，并反思特异性细胞特征如何影响免疫治疗反应或导致耐药性。该方法将为MPM的分层治疗方法和推进免疫治疗组合提供信息，以进一步改善临床结果。
Malignant pleural mesothelioma (MPM) is an incurable cancer with a dismal prognosis and few effective treatment options. Nonetheless, recent positive phase III trial results for immune checkpoint blockade (ICB) in MPM herald a new dawn in the fight to advance effective treatments for this cancer. Tumor mutation burden (TMB) has been widely reported to predict ICB in other cancers, but MPM is considered a low-TMB tumor. Similarly, tumor programmed death-ligand 1 (PD-L1) expression has not been proven predictive in phase III clinical trials in MPM. Consequently, the precise mechanisms that determine response to immunotherapy in this cancer remain unknown. The present review therefore aimed to synthesize our current understanding of the tumor immune microenvironment in MPM and reflects on how specific cellular features might impact immunotherapy responses or lead to resistance. This approach will inform stratified approaches to therapy and advance immunotherapy combinations in MPM to improve clinical outcomes further.
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