美国西奈山伊坎医学院Miriam Merad、Ephraim Kenigsberg等研究人员合作发现，对人类非小细胞肺癌病灶的单细胞分析可细化肿瘤分类和患者分层。2021年11月11日，国际知名学术期刊《癌细胞》在线发表了这一成果。

利用单细胞RNA测序，研究人员对来自35个早期非小细胞肺癌（NSCLC）病灶的361,929个细胞进行了分析。研究人员确定了一个由PDCD1⁺CXCL13⁺活化T细胞、IgG⁺浆细胞和SPP1⁺巨噬细胞组成的细胞模块，被称为肺癌激活模块（LCAM^hi）。研究人员证实了LCAM^hi在多个NSCLC队列中的富集，并通过配对CITE-seq建立了一个抗体组合来识别LCAM^hi病变。

研究人员发现LCAM的存在与整体免疫细胞含量无关，并与肿瘤突变负荷（TMB）、癌睾丸抗原和TP53突变相关。即使在TMB高于中位数的患者中，基线LCAM得分高与NSCLC对免疫疗法的反应增强相关，这表明免疫细胞组成虽然与TMB相关，但可能是对免疫疗法反应的一个非冗余生物标志物。

据介绍，免疫治疗是NSCLC治疗的主要手段。虽然TMB与免疫疗法的反应相关，但对基线免疫反应和肿瘤基因型之间的关系知之甚少。

附：英文原文

Title: Single-cell analysis of human non-small cell lung cancer lesions refines tumor classification and patient stratification

Author: Andrew M. Leader, John A. Grout, Barbara B. Maier, Barzin Y. Nabet, Matthew D. Park, Alexandra Tabachnikova, Christie Chang, Laura Walker, Alona Lansky, Jessica Le Berichel, Leanna Troncoso, Nausicaa Malissen, Melanie Davila, Jerome C. Martin, Giuliana Magri, Kevin Tuballes, Zhen Zhao, Francesca Petralia, Robert Samstein, Natalie Roy D’Amore, Gavin Thurston, Alice O. Kamphorst, Andrea Wolf, Raja Flores, Pei Wang, Sren Müller, Ira Mellman, Mary Beth Beasley, Hélène Salmon, Adeeb H. Rahman, Thomas U. Marron, Ephraim Kenigsberg, Miriam Merad

Issue&Volume: 2021-11-11

Abstract: Immunotherapy is a mainstay of non-small cell lung cancer (NSCLC) management. Whiletumor mutational burden (TMB) correlates with response to immunotherapy, little isknown about the relationship between the baseline immune response and tumor genotype.Using single-cell RNA sequencing, we profiled 361,929 cells from 35 early-stage NSCLClesions. We identified a cellular module consisting of PDCD1+CXCL13+ activated T cells, IgG+ plasma cells, and SPP1+ macrophages, referred to as the lung cancer activation module (LCAMhi). We confirmed LCAMhi enrichment in multiple NSCLC cohorts, and paired CITE-seq established an antibodypanel to identify LCAMhi lesions. LCAM presence was found to be independent of overall immune cell contentand correlated with TMB, cancer testis antigens, and TP53 mutations. High baseline LCAM scores correlated with enhanced NSCLC response to immunotherapyeven in patients with above median TMB, suggesting that immune cell composition, whilecorrelated with TMB, may be a nonredundant biomarker of response to immunotherapy.

DOI: 10.1016/j.ccell.2021.10.009

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00560-2