Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front

Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. We identified nine conserved, distinct cellular neighborhoods (CNs)-a collection of components characteristic of the CRC iTME. Enrichment of PD-1 + CD4 + T cells only within a granulocyte CN positively correlated with survival in a…

• NS
  National Science Foundation

  Award: 175329
• UD
  U.S. Department of Defense
• BA
  Bill and Melinda Gates Foundation

  Award: OPP1113682
• CR
  Cancer Research Institute
• SV
  Silicon Valley Community Foundation

  Awards: 2017-175329, 2017-177799-5022
• P
  Pfizer

  Award: 123214
• C
  Celgene

  Awards: 134073, 133826
• UO
  University of Bern
• KR
  Kenneth Rainin Foundation

  Award: 2018-575
• PI
  Parker Institute for Cancer Immunotherapy
• CR
  Cancer Research UK

  Award: C27165/A29073
• UO
  University of Oxford
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Awards: 175329, P300PB_171189, 177799, P400PM_183915
• HH
  Hamilton Health Sciences Foundation
• NI
  National Institutes of Health

  Awards: T32AI007290, CA233203, AR007422
• UF
  U.S. Food and Drug Administration
• DS
  Defence Science and Technology Laboratory
• SB
  Stanford Bio-X
• JT
  Juno Therapeutics