Spatial immunophenotyping of the tumour microenvironment in non–small cell lung cancer

CD8型 免疫系统 细胞毒性T细胞 生物 肿瘤微环境 免疫分型 癌症研究 自然杀伤性T细胞 CD38 免疫学 细胞生物学 抗原 干细胞 川地34 体外 生物化学
作者
Max Backman,Carina Strell,Amanda Lindberg,Johanna Sofia Margareta Mattsson,Hedvig Elfving,Hans Brunnström,Aine O’Reilly,Martina Bosić,Miklós Gulyás,Johan Isaksson,Johan Botling,Klas Kärre,Karin Jirström,Kristina Lamberg,Fredrik Pontén,Karin Leandersson,Artur Mezheyeuski,Patrick Micke
出处
期刊:European Journal of Cancer [Elsevier BV]
卷期号:185: 40-52 被引量:26
标识
DOI:10.1016/j.ejca.2023.02.012
摘要

IntroductionImmune cells in the tumour microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterise the spatial immune phenotypes in the mutational and clinicopathological background of non–small cell lung cancer (NSCLC).MethodsWe established a multiplexed fluorescence imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4-Eff), CD4 regulatory cells (CD4-Treg), CD8 effector cells (CD8-Eff), CD8 regulatory cells (CD8-Treg), B-cells, natural killer cells, natural killer T-cells, M1 macrophages (M1), CD163+ myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs).ResultsCD4-Eff cells, CD8-Eff cells and M1 macrophages were the most abundant immune cells invading the tumour cell compartment and indicated a patient group with a favourable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4-Eff, CD4-Treg, CD8-Treg, B-cells and pDCs) were independently associated with longer survival. However, when these immune cells were located close to CD8-Treg cells, the favourable impact was attenuated. In the multivariable Cox regression model, including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8-Treg–B-cells, CD8-Eff–cancer cells and B-cells–CD4-Treg) demonstrated positive prognostic impact, whereas short M2–M1 distances were prognostically unfavourable.ConclusionWe present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is crucial for diagnostic use.
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