Abstract
SummaryAntitumoral 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 high-risk patient subset. Coupling of tumor and immune CNs, fragmentation of T cell and macrophage CNs, and disruption of inter-CN communication was associated with inferior outcomes. This study provides a framework for interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions of cells and spatial domains.
Highlights
The immune tumor microenvironment is a complex assembly of tumor, immune, stromal, and extracellular components
1344 Cell 182, 1341–1359, September 3, 2020 ll further, we found that the Ki-67+CD8+ T cell density in the T cellenriched cellular neighborhoods (CNs) was anti-correlated with the frequency of regulatory T (Treg) cells in the macrophage-enriched CN in diffuse inflammatory infiltration (DII) but not Crohn’s-like reaction’’ (CLR) patients
These data demonstrate that FFPE-optimized co-detection by indexing (CODEX) is suitable for highly multiplexed single-cell marker visualization, quantification and biomarker discovery in clinically relevant tissues
Summary
The immune tumor microenvironment (iTME) is a complex assembly of tumor, immune, stromal, and extracellular components Organization of these components at the cellular and tissue levels plays a crucial role in the effectiveness of antitumor immunity (Binnewies et al, 2018). We demonstrated that the identity of cells could often be predicted by their neighbors, implying mutual information relationships that link cell marker expression and tissue localization. These neighbor relationships were predictive of disease progression in a murine model of autoimmunity (Goltsev et al, 2018). To better study the iTME in cancer patients with long-term clinical follow-up, including survival data, we re-engineered the CODEX method to be compatible with formalin-fixed, paraffinembedded (FFPE) tissue and tissue microarrays (TMAs)
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