SSRN Electronic Journal · 2019 · 17 citations · 0 references
MedicineImmunologyOncologyCancer ImmunologyTumor ImmunologyTumor MicroenvironmentAntitumor T Cell ResponsesT Cell Responses To TumorsTumor Immune MicroenvironmentTumor Microenvironment InteractionsTumor-associated MacrophagesTumor-infiltrating LymphocytesCd4 Positive T CellsColorectal Cancer PrognosisCoordinated InteractionImmune Biomarker ProfilingImmune Landscape ProfilingTissue MicroarraysTumor Immune Microenvironment ProfilingTumor-immune Crosstalk
Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). The study aims to understand coordinated immune behavior in effective versus ineffective tumor control and to provide a framework for interrogating antitumoral immunity through concerted cellular actions. We re‑engineered CODEX for paraffin‑embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced‑stage colorectal cancer patients with 56 protein markers. Nine conserved cellular neighborhoods were identified, with PD‑1+CD4+ T‑cell enrichment in a granulocyte neighborhood correlating with survival in high‑risk patients, while disrupted coupling and fragmentation of tumor and immune neighborhoods and loss of inter‑neighborhood communication were linked to poorer outcomes.
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 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.