Data from Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial

无容量 免疫系统 易普利姆玛 医学 FOXP3型 抗体 内科学 免疫疗法 肿瘤科 癌症研究 免疫学
作者
Edwin R. Parra,Jiexin Zhang,Dzifa Y. Duose,Edgar Gonzalez‐Kozlova,Mary W. Redman,Hong Chen,Ganiraju C. Manyam,Gayatri Kumar,Jianhua Zhang,Xingzhi Song,Rossana Lazcano,Mario L. Marques‐Piubelli,Caddie Laberiano-Fernández,Frank Rojas,Baili Zhang,Len Taing,Aashna Jhaveri,Jacob Geisberg,Jennifer Altreuter,Franziska Michor,James Provencher,Joyce Yu,Ethan Cerami,Radim Moravec,Kasthuri Kannan,Rajyalakshmi Luthra,Gheath Alatrash,Hsin-Hui Huang,Hui Xie,Manishkumar Patel,Ke Nie,Jocelyn Harris,Kimberly Argueta,James Lindsay,Roshni Biswas,Stephen Van Nostrand,Seunghee Kim‐Schulze,Jhanelle E. Gray,Roy S. Herbst,Ignacio I. Wistuba,Scott Gettinger,Karen Kelly,Lyudmila Bazhenova,Sacha Gnjatic,John Lee,Jianjun Zhang,Cara Haymaker
标识
DOI:10.1158/1078-0432.c.7181344
摘要

<div>AbstractPurpose:<p>Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need.</p>Experimental Design:<p>Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non–small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink.</p>Results:<p>Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with <i>LRP1B</i>-mutant tumors had a shorter survival than patients with <i>LRP1B</i>-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression.</p>Conclusions:<p>The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC.</p></div>
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