研究动态
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结直肠癌中 CD274(PD-L1)/PDCD1(PD-1) 免疫检查点表达和巨噬细胞极化的空间分辨率多标记评估。

Spatially resolved multimarker evaluation of CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint expression and macrophage polarisation in colorectal cancer.

发表日期:2023 Mar 31
作者: Hanna Elomaa, Maarit Ahtiainen, Sara A Väyrynen, Shuji Ogino, Jonathan A Nowak, Mai Chan Lau, Olli Helminen, Erkki-Ville Wirta, Toni T Seppälä, Jan Böhm, Jukka-Pekka Mecklin, Teijo Kuopio, Juha P Väyrynen
来源: BRITISH JOURNAL OF CANCER

摘要:

CD274(PD-L1)/PDCD1(PD-1)免疫检查点相互作用可能促进癌症进展,但PD-L1和PD-1在结直肠癌微环境中的表达模式和预后意义还不够清晰。我们使用定制的9重免疫组化方法,在910名结直肠癌患者中量化PD-L1和PD-1在巨噬细胞、T细胞和肿瘤细胞中的表达模式。我们利用多元Cox回归模型根据免疫细胞亚群密度评估癌症特异性死亡率。与PD-L1-巨噬细胞相比,PD-L1+巨噬细胞更可能是M1极化,位于靠近肿瘤细胞的位置。浸润边缘的PD-L1+巨噬细胞密度与较长的癌症特异性生存相关[Ptrend = 0.0004,最高第四分位数与最低第一分位数相比的HR为0.52;95%CI:0.34-0.78]。无论PD-1表达如何,T细胞密度与较长的癌症特异性生存相关(PD-1+和PD-1-细胞亚群的Ptrend  <  0.005)。PD-1+ T细胞/PD-L1+巨噬细胞簇的高密度与较长的癌症特异性生存相关(Ptrend  <  0.005)。PD-L1+巨噬细胞表现出独特的极化特征(更像M1型)、空间特征(与肿瘤细胞和PD-1+ T细胞更多共局),并与有利的临床结果相关。我们的全面多标记评估可以增进对肿瘤微环境中免疫检查点的理解,促进改进免疫治疗的发展。 ©2023作者。
The CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint interaction may promote cancer progression, but the expression patterns and prognostic significance of PD-L1 and PD-1 in the colorectal cancer microenvironment are inadequately characterised.We used a custom 9-plex immunohistochemistry assay to quantify the expression patterns of PD-L1 and PD-1 in macrophages, T cells, and tumour cells in 910 colorectal cancer patients. We evaluated cancer-specific mortality according to immune cell subset densities using multivariable Cox regression models.Compared to PD-L1- macrophages, PD-L1+ macrophages were more likely M1-polarised than M2-polarised and located closer to tumour cells. PD-L1+ macrophage density in the invasive margin associated with longer cancer-specific survival [Ptrend = 0.0004, HR for the highest vs. lowest quartile, 0.52; 95% CI: 0.34-0.78]. T cell densities associated with longer cancer-specific survival regardless of PD-1 expression (Ptrend < 0.005 for both PD-1+ and PD-1- subsets). Higher densities of PD-1+ T cell/PD-L1+ macrophage clusters associated with longer cancer-specific survival (Ptrend < 0.005).PD-L1+ macrophages show distinct polarisation profiles (more M1-like), spatial features (greater co-localisation with tumour cells and PD-1+ T cells), and associations with favourable clinical outcome. Our comprehensive multimarker assessment could enhance the understanding of immune checkpoints in the tumour microenvironment and promote the development of improved immunotherapies.© 2023. The Author(s).