Efficient expansion of XCR1+CD141+ cDC1 cells from human PBMCs: a promising strategy for DC-based vaccine

Abstract

Dendritic cells (DCs) are pivotal orchestrators of immune activation, serving as professional antigen-presenting cells that bridge innate and adaptive immunity. Among them, conventional type 1 dendritic cells (cDC1s) play a critical role in initiating cytotoxic T-cell responses and anti-tumor immunity. Despite their therapeutic promise, the clinical translation of cDC1-based vaccines has been limited by challenges in large-scale in vitro generation. Here, we established an efficient and reproducible two-step protocol for producing functional XCR1⁺ CD141⁺ cDC1s from human peripheral blood mononuclear cells (PBMCs), providing a practical and potentially scalable approach for cell sourcing. Transcriptomic profiling confirmed strong expression of cDC1 lineage markers and revealed that mature cDC1s exhibit pronounced activation of immune-related pathways and secretion of key cytokines and chemokines involved in immune modulation. Functionally, the generated cDC1s effectively primed antigen-specific cytotoxic T lymphocytes (CTLs), which exhibited significantly enhanced IFN-γ production and tumor cell cytotoxicity compared with both control T cells and monocyte-derived DC–induced CTLs (moDC-CTLs). Importantly, preclinical evaluation in NOG mice showed no treatment-related toxicity, providing preliminary—though model-limited—safety evidence for this approach. Collectively, these findings establish an efficient and reproducible strategy for generating human cDC1s and highlight their potential as a candidate platform for dendritic cell–based cancer immunotherapy.