Yoon Kyung Jeon, Jaemoon Koh, Dongjoo Lee, Sehui Kim, Seung Geun Song, Bogyeong Han, Hyein Jeong, Young A Kim, Bhumsuk Keam, Se-Hoon Lee, Kwangsoo Kim, Doo Hyun Chung
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引用次数: 0
摘要
肿瘤细胞(TC)上的PD-L1表达被用作肺癌的免疫治疗生物标记物,但经常观察到肿瘤内的异质性表达。我们利用数字空间剖析技术,根据肿瘤 PD-L1 的表达和免疫微环境的状况,对空间匹配区域的肿瘤细胞和免疫细胞(IC)进行了蛋白质组和全转录组分析。我们的研究结果得到了免疫组化、癌症基因组图谱和免疫疗法队列的验证。TC上PD-L1高表达区域的IC比TC上PD-L1低表达区域的IC显示出更多表明免疫抑制和衰竭的特征。免疫炎症(IF)区内高表达 PD-L1 的 TC 显示了促炎过程的上调,而免疫缺陷(ID)区内高表达 PD-L1 的 TC 则显示了各种代谢过程的上调。利用IF和ID区域TC的差异表达基因,我们发现了肺癌的新型预后基因特征。此外,我们还发现,CD8+细胞与M2巨噬细胞的高比例可预测PD-L1表达的肺癌患者在接受免疫检查点抑制剂治疗后的良好预后。这项研究表明,TC 和 IC 在肿瘤微环境中具有不同的空间特征,这些特征与肿瘤 PD-L1 表达和 IC 浸润有关。
Spatially resolved whole-transcriptomic and proteomic profiling of lung cancer and its immune-microenvironment according to PD-L1 expression.
The expression of PD-L1 on tumor cells (TCs) is used as an immunotherapy biomarker in lung cancer, but heterogeneous intratumoral expression is often observed. Using a Digital Spatial Profiling, we performed proteomic and whole-transcriptomic analyses of TCs and immune cells (ICs) in spatially matched areas based on tumor PD-L1 expression and the status of the immune microenvironment. Our findings were validated using immunohistochemistry, The Cancer Genome Atlas, and immunotherapy cohorts. ICs in areas with high PD-L1 expression on TCs showed more features indicative of immunosuppression and exhaustion than ICs in areas with low PD-L1 expression on TCs. TCs highly expressing PD-L1 within immune-inflamed (IF) areas show up-regulation of pro-inflammatory processes, whereas TCs highly expressing PD-L1 within immune-deficient (ID) areas show up-regulation of various metabolic processes. Using differentially expressed genes of TCs between the IF and ID areas, we identified a novel prognostic gene signature for lung cancer. In addition, a high ratio of CD8+ cells to M2 macrophages was found to predict favorable outcomes in patients with PD-L1-expressing lung cancer after immune checkpoint inhibitor therapy. This study demonstrates that TCs and ICs have distinct spatial features within the tumor microenvironment that are related to tumor PD-L1 expression and IC infiltration.
期刊介绍:
Cancer Immunology Research publishes exceptional original articles showcasing significant breakthroughs across the spectrum of cancer immunology. From fundamental inquiries into host-tumor interactions to developmental therapeutics, early translational studies, and comprehensive analyses of late-stage clinical trials, the journal provides a comprehensive view of the discipline. In addition to original research, the journal features reviews and opinion pieces of broad significance, fostering cross-disciplinary collaboration within the cancer research community. Serving as a premier resource for immunology knowledge in cancer research, the journal drives deeper insights into the host-tumor relationship, potent cancer treatments, and enhanced clinical outcomes.
Key areas of interest include endogenous antitumor immunity, tumor-promoting inflammation, cancer antigens, vaccines, antibodies, cellular therapy, cytokines, immune regulation, immune suppression, immunomodulatory effects of cancer treatment, emerging technologies, and insightful clinical investigations with immunological implications.