人 CD34(+) 来源的浆细胞样树突状细胞作为原代 pDC 的替代物及潜在的肿瘤免疫治疗

We designed an in vitro differentiation protocol tailored for human pDCs from cord blood (CB) hematopoietic stem cells (HSCs) with StemRegenin 1 (SR-1) and GM-CSF supplementation. Next, we evaluated the identity and function of CB-pDCs compared to human primary pDCs. Furthermore, we tested the potential of CB-pDCs to support anti-tumor immune responses in co-culture with tumor explants from CRC patients.

Here, we report an in vitro differentiation protocol enabling the generation of 200 pDCs per HSC and highlight the role of GM-CSF and SR-1 in CB-pDC differentiation and function. CB-pDCs exhibited a robust resemblance to primary pDCs phenotypically and functionally. Transcriptomic analysis confirmed strong homology at both, baseline and upon TLR9 or TLR7 stimulation. Further, we could confirm the potential of CB-pDCs to promote inflammation in the tumor microenvironment by eliciting cytokines associated with NK and T cell recruitment and function upon TLR7 stimulation ex vivo in patient tumor explants. DISCUSSION: This study highlights CB-pDCs as surrogates for primary pDCs to investigate their biology and for their potential use as cell therapy in cancer.