Cui Yang, Zhang Weihang, Zeng Xin, Yang Yitao, Park Sung-Joon, Nakai Kenta
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Front Immunol. 2024 Nov 27;15:1497251. doi: 10.3389/fimmu.2024.1497251. eCollection 2024.
The tumor microenvironment (TME) plays a crucial role in tumor progression and immunoregulation. Major histocompatibility complex class II (MHC-II) is essential for immune surveillance within the TME. While MHC-II genes are typically expressed by professional antigen-presenting cells, they are also expressed in tumor cells, potentially facilitating antitumor immune responses. To understand the role of MHC-II-expressing tumor cells, we analyzed triple-negative breast cancer (TNBC), an aggressive subtype with poor prognosis and limited treatment options, using public bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomics datasets. Our analysis revealed a distinct tumor subpopulation that upregulates MHC-II genes and actively interacts with immune cells. We implicated that this subpopulation is preferentially present in proximity to regions in immune infiltration of TNBC patient cohorts with a better prognosis, suggesting the functional importance of MHC-II-expressing tumor cells in modulating the immune landscape and influencing patient survival outcomes. Remarkably, we identified a prognostic signature comprising 40 significant genes in the MHC-II-expressing tumors in which machine leaning models with the signature successfully predicted patient survival outcomes and the degree of immune infiltration. This study advances our understanding of the immunological basis of cancer progression and suggests promising new directions for therapeutic strategies.
肿瘤微环境（TME）在肿瘤进展和免疫调节中起着关键作用。主要组织相容性复合体II类（MHC-II）对于TME内的免疫监视至关重要。虽然MHC-II基因通常由专职抗原呈递细胞表达，但它们也在肿瘤细胞中表达，这可能促进抗肿瘤免疫反应。为了了解表达MHC-II的肿瘤细胞的作用，我们使用公开的批量RNA测序、单细胞RNA测序和空间转录组学数据集，分析了三阴性乳腺癌（TNBC），这是一种侵袭性亚型，预后较差且治疗选择有限。我们的分析揭示了一个独特的肿瘤亚群，该亚群上调MHC-II基因并与免疫细胞积极相互作用。我们认为这个亚群优先存在于预后较好的TNBC患者队列免疫浸润区域附近，这表明表达MHC-II的肿瘤细胞在调节免疫格局和影响患者生存结果方面具有功能重要性。值得注意的是，我们在表达MHC-II的肿瘤中鉴定出一个由40个显著基因组成的预后特征，其中具有该特征的机器学习模型成功预测了患者的生存结果和免疫浸润程度。这项研究推进了我们对癌症进展免疫基础的理解，并为治疗策略提出了有前景的新方向。
