학술논문

Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity
Document Type
article
Source
Cancer Cell. 26(5)
Subject
Biomedical and Clinical Sciences
Oncology and Carcinogenesis
Immunology
Genetics
Cancer
Underpinning research
1.1 Normal biological development and functioning
Inflammatory and immune system
Animals
Antigens
CD
Coculture Techniques
Dendritic Cells
Female
Humans
Immunotherapy
Adoptive
Macrophages
Mammary Neoplasms
Experimental
Mice
Inbred C57BL
Myeloid Cells
T-Lymphocytes
Tumor Cells
Cultured
Tumor Microenvironment
Neurosciences
Oncology & Carcinogenesis
Biochemistry and cell biology
Oncology and carcinogenesis
Language
Abstract
It is well understood that antigen-presenting cells (APCs) within tumors typically do not maintain cytotoxic T cell (CTL) function, despite engaging them. Across multiple mouse tumor models and human tumor biopsies, we have delineated the intratumoral dendritic cell (DC) populations as distinct from macrophage populations. Within these, CD103(+) DCs are extremely sparse and yet remarkably capable CTL stimulators. These are uniquely dependent on IRF8, Zbtb46, and Batf3 transcription factors and are generated by GM-CSF and FLT3L cytokines. Regressing tumors have higher proportions of these cells, T-cell-dependent immune clearance relies on them, and abundance of their transcripts in human tumors correlates with clinical outcome. This cell type presents opportunities for prognostic and therapeutic approaches across multiple cancer types.