华中科技大学孙朝阳等研究人员合作发现，宫颈鳞状细胞癌的多组学分析确定具有生物学和临床意义的细胞生态系统。相关论文于2023年11月20日在线发表在《自然—遗传学》杂志上。

研究人员进行了一项多组学分析，包括单细胞RNA测序、空间转录组学和空间蛋白质组学，并结合遗传学和药理学扰动，系统地绘制了一张高分辨率和空间分辨的宫颈鳞状细胞癌（CSCC）瘤内表达异质性图谱。三种肿瘤状态（上皮-细胞角蛋白、上皮-免疫（Epi-Imm）和上皮衰老）再现了鳞状细胞分化的不同阶段，显示出不同的肿瘤免疫微环境。上皮-细胞角蛋白恶性细胞与免疫抑制性癌相关成纤维细胞之间的双向相互作用通过FABP5介导的转化生长因子β通路信号形成了免疫排斥性微环境。在Epi-Imm肿瘤中，恶性细胞通过干扰素信号与自然杀伤细胞和T细胞相互作用。对一项宫颈癌临床试验（NCT04516616）样本的初步分析表明，新辅助化疗会诱导肿瘤向Epi-Imm状态转变，这与免疫检查点阻断剂治疗后的病理完全缓解相关。这些发现加深了人们对CSCC细胞状态多样性的理解。

研究人员表示，CSCC对免疫检查点阻断的反应有限。

附：英文原文

Title: Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance

Author: Fan, Junpeng, Lu, Funian, Qin, Tianyu, Peng, Wenju, Zhuang, Xucui, Li, Yinuo, Hou, Xin, Fang, Zixuan, Yang, Yunyi, Guo, Ensong, Yang, Bin, Li, Xi, Fu, Yu, Kang, Xiaoyan, Wu, Zimeng, Han, Lili, Mills, Gordon B., Ma, Xiangyi, Li, Kezhen, Wu, Peng, Ma, Ding, Chen, Gang, Sun, Chaoyang

Issue&Volume: 2023-11-20

Abstract: Cervical squamous cell carcinoma (CSCC) exhibits a limited response to immune-checkpoint blockade. Here we conducted a multiomic analysis encompassing single-cell RNA sequencing, spatial transcriptomics and spatial proteomics, combined with genetic and pharmacological perturbations to systematically develop a high-resolution and spatially resolved map of intratumoral expression heterogeneity in CSCC. Three tumor states (epithelial-cytokeratin, epithelial-immune (Epi-Imm) and epithelial senescence), recapitulating different stages of squamous differentiation, showed distinct tumor immune microenvironments. Bidirectional interactions between epithelial-cytokeratin malignant cells and immunosuppressive cancer-associated fibroblasts form an immune exclusionary microenvironment through transforming growth factor β pathway signaling mediated by FABP5. In Epi-Imm tumors, malignant cells interact with natural killer and T cells through interferon signaling. Preliminary analysis of samples from a cervical cancer clinical trial (NCT04516616) demonstrated neoadjuvant chemotherapy induces a state transition to Epi-Imm, which correlates with pathological complete remission following treatment with immune-checkpoint blockade. These findings deepen the understanding of cellular state diversity in CSCC.

DOI: 10.1038/s41588-023-01570-0

Source: https://www.nature.com/articles/s41588-023-01570-0