美国纪念斯隆-凯特琳癌症中心Charles M. Rudin、Dana Pe'er等研究人员合作揭示人类小细胞肺癌图谱中的可塑性、转移性和免疫抑制特征。2021年10月14日，国际知名学术期刊《癌细胞》在线发表了这一成果。

据研究人员介绍，SCLC是一种侵袭性恶性肿瘤，包括由ASCL1、NEUROD1和POU2F3的不同表达所定义的亚型，分别为SCLC-A、-N和-P。

为了确定不同亚型的肿瘤及其相关微环境的异质性，研究人员对21个人类生物样本的155,098个转录组进行了测序，包括54,523个小细胞肺癌（SCLC）转录组。研究人员观察到SCLC的肿瘤多样性比肺腺癌更大，由典型、中间和混合亚型驱动。研究人员发现了一种PLCG2高的SCLC表型，具有干性、促转移的特征，在各亚型中反复出现，并预测总生存期会变差。与肺腺癌相比，SCLC表现出更大的免疫隔离和更少的免疫浸润，SCLC-N比SCLC-A表现出更少的免疫浸润和更大的T细胞功能障碍。研究人员在SCLC肿瘤中发现了一个顺应性、免疫抑制性的单核细胞/巨噬细胞群体，它与复发型PLCG2高的亚群特别相关。

附：英文原文

Title: Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer

Author: Joseph M. Chan, álvaro Quintanal-Villalonga, Vianne Ran Gao, Yubin Xie, Viola Allaj, Ojasvi Chaudhary, Ignas Masilionis, Jacklynn Egger, Andrew Chow, Thomas Walle, Marissa Mattar, Dig V.K. Yarlagadda, James L. Wang, Fathema Uddin, Michael Offin, Metamia Ciampricotti, Besnik Qeriqi, Amber Bahr, Elisa de Stanchina, Umesh K. Bhanot, W. Victoria Lai, Matthew J. Bott, David R. Jones, Arvin Ruiz, Marina K. Baine, Yanyun Li, Natasha Rekhtman, John T. Poirier, Tal Nawy, Triparna Sen, Linas Mazutis, Travis J. Hollmann, Dana Peer, Charles M. Rudin

Issue&Volume: 2021-10-14

Abstract: Small cell lung cancer (SCLC) is an aggressive malignancy that includes subtypes definedby differential expression of ASCL1, NEUROD1, and POU2F3 (SCLC-A, -N, and -P, respectively). To define the heterogeneity of tumors and theirassociated microenvironments across subtypes, we sequenced 155,098 transcriptomesfrom 21 human biospecimens, including 54,523 SCLC transcriptomes. We observe greatertumor diversity in SCLC than lung adenocarcinoma, driven by canonical, intermediate,and admixed subtypes. We discover a PLCG2-high SCLC phenotype with stem-like, pro-metastatic features that recurs across subtypesand predicts worse overall survival. SCLC exhibits greater immune sequestration andless immune infiltration than lung adenocarcinoma, and SCLC-N shows less immune infiltrateand greater T cell dysfunction than SCLC-A. We identify a profibrotic, immunosuppressivemonocyte/macrophage population in SCLC tumors that is particularly associated withthe recurrent, PLCG2-high subpopulation.

DOI: 10.1016/j.ccell.2021.09.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00497-9