Frontiers in immunology · 2026
Identification of heterogeneous subtypes of human dendritic cells from the lymph nodes of patients with gastric cancer.
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Han Song-Hee, Lee In-Jeong, Tran Hue Vy An, Joo Mi Ha, Kim Kwan Woo, Kim JungMo, Kim Seung Ho, Woo Hyun Goo, Kim Min Chan, Kwak Jong-Young
Аннотация
OBJECTIVE: The subtypes of heterogeneous conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) in lymph nodes (LN) cannot be distinguished because they share similar surface markers. This study aimed to identify cDCs, pDCs, and other cell types in DC-enriched LNs from patients with gastric cancer (GC) by analyzing surface markers and gene expression.
METHODS: Expression of surface markers, including CD141, CD1c, and CD123, in DC-enriched cells was analyzed by conventional flow cytometry and AbSeq using antibody-derived tags. Transcriptome and epitope analyses were used to characterize DC subtypes. The frequencies of heterogeneous DC subtypes were compared across clinical stages and molecular subtypes in patients with GC.
RESULTS: DC-enriched cells showed CD1c+CD141+ and CD141+CD123+ populations. A clustering approach based on antibody-derived tags identified 17 clusters with single- and double-positive DC surface markers. Transcriptome and epitope analyses identified 26 clusters with distinct surface markers and gene expression profiles. DC lineages included subtypes distinct from the typical cDC1, cDC2, and pDC types. A proportion of CD1c-expressing cDC2 lineage cells expressed surface features characteristic of cDC1 and pDC, and CD1c expression was observed in cell types other than DC lineages. Differences in DC cluster frequencies across DC lineages were not detected as significant across clinical stages and molecular subtypes of GC. The mRNA expression pattern in the CD141+ cDC1 lineage distinguished it from the CD1c+ cDC2 lineage and resolved different clusters with transitional states within both lineages. Transcripts related to DC maturation and migration were detected in a CD137-DC subtype, which highly expressed HLA-DR and CD137.
CONCLUSION: Cluster analysis of DC-enriched cells in LNs from our integrated dataset revealed subtypes of the cDC1, cDC2, and pDC lineages. We identified distinctive DC subtypes in the transitional state bridging differentiation between cDC1 and cDC2. CD137-DC may be an independent DC subset with mature and migratory features.
METHODS: Expression of surface markers, including CD141, CD1c, and CD123, in DC-enriched cells was analyzed by conventional flow cytometry and AbSeq using antibody-derived tags. Transcriptome and epitope analyses were used to characterize DC subtypes. The frequencies of heterogeneous DC subtypes were compared across clinical stages and molecular subtypes in patients with GC.
RESULTS: DC-enriched cells showed CD1c+CD141+ and CD141+CD123+ populations. A clustering approach based on antibody-derived tags identified 17 clusters with single- and double-positive DC surface markers. Transcriptome and epitope analyses identified 26 clusters with distinct surface markers and gene expression profiles. DC lineages included subtypes distinct from the typical cDC1, cDC2, and pDC types. A proportion of CD1c-expressing cDC2 lineage cells expressed surface features characteristic of cDC1 and pDC, and CD1c expression was observed in cell types other than DC lineages. Differences in DC cluster frequencies across DC lineages were not detected as significant across clinical stages and molecular subtypes of GC. The mRNA expression pattern in the CD141+ cDC1 lineage distinguished it from the CD1c+ cDC2 lineage and resolved different clusters with transitional states within both lineages. Transcripts related to DC maturation and migration were detected in a CD137-DC subtype, which highly expressed HLA-DR and CD137.
CONCLUSION: Cluster analysis of DC-enriched cells in LNs from our integrated dataset revealed subtypes of the cDC1, cDC2, and pDC lineages. We identified distinctive DC subtypes in the transitional state bridging differentiation between cDC1 and cDC2. CD137-DC may be an independent DC subset with mature and migratory features.