PT  - JOURNAL ARTICLE
AU  - Andrew M. Leader
AU  - John A. Grout
AU  - Christie Chang
AU  - Barbara Maier
AU  - Alexandra Tabachnikova
AU  - Laura Walker
AU  - Alona Lansky
AU  - Jessica LeBerichel
AU  - Naussica Malissen
AU  - Melanie Davila
AU  - Jerome Martin
AU  - Giuliana Magri
AU  - Kevin Tuballes
AU  - Zhen Zhao
AU  - Francesca Petralia
AU  - Robert Samstein
AU  - Natalie Roy D’Amore
AU  - Gavin Thurston
AU  - Alice Kamphorst
AU  - Andrea Wolf
AU  - Raja Flores
AU  - Pei Wang
AU  - Mary Beth Beasley
AU  - Helene Salmon
AU  - Adeeb H. Rahman
AU  - Thomas U. Marron
AU  - Ephraim Kenigsberg
AU  - Miriam Merad
TI  - CITEseq analysis of non-small-cell lung cancer lesions reveals an axis of immune cell activation associated with tumor antigen load and <em>TP53</em> mutations
AID  - 10.1101/2020.07.16.207605
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.16.207605
4099  - http://biorxiv.org/content/early/2020/07/17/2020.07.16.207605.short
4100  - http://biorxiv.org/content/early/2020/07/17/2020.07.16.207605.full
AB  - Immunotherapy is becoming a mainstay in the treatment of NSCLC. While tumor mutational burden (TMB) has been shown to correlate with response to immunotherapy, little is known about the relation of the baseline immune response with the tumor genotype. Here, we profiled 35 early stage NSCLC lesions using multiscale single cell sequencing. Unsupervised clustering identified in a subset of patients a key cellular module consisting of PDCD1+ CXCL13+ activated T cells, IgG+ plasma cells, and SPP1+ macrophages, referred to as the lung cancer activation module (LCAMhi). Transcriptional data from two NSCLC cohorts confirmed a subset of patients with LCAMhi enrichment, which was independent of overall immune cell content. The LCAMhi module strongly correlated with TMB, expression of cancer testis antigens, and with TP53 mutations in smokers and non-smokers. These data establish LCAM as a key mode of immune cell activation associated with high tumor antigen load and driver mutations.Competing Interest StatementResearch support for this work was provided by Regeneron and Takeda. The authors declare no other competing financial interests.