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

• DOI: 10.1016/j.ccell.2021.09.008
• Publication Date: 2021-10-16T03:19:24Z
• Authors: Joseph M. Chan; Álvaro Quintanal-...; 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 Pe'er; Charles M. Rudin
• Keywords: CD163; Immunosuppression

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