| Literature DB >> 34767762 |
Andrew M Leader1, John A Grout1, Barbara B Maier1, Barzin Y Nabet2, Matthew D Park1, Alexandra Tabachnikova1, Christie Chang3, Laura Walker3, Alona Lansky1, Jessica Le Berichel1, Leanna Troncoso1, Nausicaa Malissen4, Melanie Davila3, Jerome C Martin5, Giuliana Magri1, Kevin Tuballes3, Zhen Zhao6, Francesca Petralia7, Robert Samstein8, Natalie Roy D'Amore9, Gavin Thurston10, Alice O Kamphorst1, Andrea Wolf11, Raja Flores11, Pei Wang7, Sören Müller12, Ira Mellman13, Mary Beth Beasley6, Hélène Salmon1, Adeeb H Rahman14, Thomas U Marron15, Ephraim Kenigsberg16, Miriam Merad17.
Abstract
Immunotherapy is a mainstay of non-small cell lung cancer (NSCLC) management. While tumor mutational burden (TMB) correlates with response to immunotherapy, little is known 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 NSCLC lesions. 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 antibody panel to identify LCAMhi lesions. LCAM presence was found to be independent of overall immune cell content and correlated with TMB, cancer testis antigens, and TP53 mutations. High baseline LCAM scores correlated with enhanced NSCLC response to immunotherapy even in patients with above median TMB, suggesting that immune cell composition, while correlated with TMB, may be a nonredundant biomarker of response to immunotherapy.Entities:
Keywords: CITEseq; NSCLC; dendritic cells; high dimensional profiling; immunotherapy; macrophages; tumor cell atlas; tumor microenvironment; tumor mutational burden; tumor-associated myeloid cells
Mesh：
Year: 2021 PMID： 34767762 PMCID： PMC8728963 DOI： 10.1016/j.ccell.2021.10.009
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743