免疫蛋白酶体在固体肿瘤中的预后关系受到即时免疫环境的支配。
Prognostic association of immunoproteasome expression in solid tumours is governed by the immediate immune environment.
发表日期:2023 Apr 25
作者:
Rahul Kumar, Bhavya Dhaka, Sarthak Sahoo, Mohit Kumar Jolly, Radhakrishnan Sabarinathan
来源:
Molecular Oncology
摘要:
肿瘤细胞诱导免疫蛋白酶体(IP)表达可以增强抗原呈递和免疫原性。最近在黑色素瘤中,IP基因的过度表达与更好的预后和免疫检查点阻断(ICB)疗法的反应有关。然而,这种关联在其他实体肿瘤中的程度以及它如何受肿瘤细胞内在因素和细胞外因素的影响尚不清楚。在这里,我们通过探索原始肿瘤的可用的批量和单细胞转录组数据的基因表达模式来深入研究。我们发现高IP表达的肿瘤表现出细胞毒性免疫细胞浸润和肿瘤细胞中IFN-γ和TNF-α途径的上调。但是,IP表达与总体生存率(TCGA队列)和ICB疗法的反应(非TCGA队列)的关联是肿瘤类型特异性的(非小细胞肺癌、乳腺癌、膀胱癌和胸腺瘤更好;而在胶质瘤和肾脏中更糟)。这在很大程度上取决于激烈的免疫细胞浸润模式是促进还是抑制肿瘤。这强调了需要考虑免疫细胞浸润模式和IP表达作为预测固体肿瘤总体生存率或ICB疗法反应的预后生物标志物,而不仅仅是在黑色素瘤。本文章受版权保护。保留所有权利。
Induction of immunoproteasome (IP) expression in tumour cells can enhance antigen presentation and immunogenicity. Recently, overexpression of IP genes has been associated with better prognosis and response to immune checkpoint blockade (ICB) therapies in melanoma. However, the extent of this association in other solid tumours and how that is influenced by tumour cell-intrinsic and cell-extrinsic factors remains unclear. Here, we address this by exploring the gene expression patterns from available bulk and single-cell transcriptomic data of primary tumours. We find that tumours with high IP expression exhibit cytotoxic immune cell infiltration and upregulation of IFN-γ and TNF-α pathways in tumour cells. However, the association of IP expression with overall survival (TCGA cohort) and response to ICB therapy (non-TCGA cohorts) is tumour-type specific (better in non-small-cell lung, breast, bladder, and thymus; and worse in glioma and renal) and is greatly influenced by pro- or anti-tumorigenic immune cell infiltration patterns. This emphasises the need for considering immune cell infiltration patterns, along with IP expression, as a prognostic biomarker to predict overall survival or response to ICB therapies in solid tumours, besides melanoma.This article is protected by copyright. All rights reserved.