Background/Objectives: This study aimed to characterize dendritic cell (DC) heterogeneity, immune associations, and prognostic relevance across threeTP53-mutated tumor entities—high-grade serous ovarian cancer (HGSOC), triple-negative breast cancer, and endometrial cancer—focusing on plasmacytoid DCs (pDCs) in HGSOC.Methods: RNA-sequencing and clinical data of 603 patients from The Cancer Genome Atlas were analyzed. DC subset abundance was assessed for cDC progenitor, conventional DC type 1 (cDC1), conventional DC type 2 (cDC2), plasmacytoid DC (pDC), and mature DC by marker gene signatures. Differences in DC scores across tumors were analyzed using Kruskal–Wallis. Survival analyses were performed using Kaplan–Meier and Cox regression. Spearman’s correlation was used to determine associations between parameters.Results: HGSOC showed the lowest pDC abundance, yet high pDC scores were independently associated with shorter PFS (HR = 1.55, 95% CI: 1.05–2.27;p= 0.027), representing the only DC-subset-related prognostic signal observed across tumor types. pDCs correlated positively with neutrophils and negatively with monocytes, and pDCs, cDC2s, and cDC progenitors correlated inversely with TMB. No consistent link was found between pDC andTP53mutation classes. However, tumors harboring specificTP53mutations within established hotspot regions exhibited significantly lower pDC levels (p= 0.015).Conclusions: Our findings reveal distinct DC infiltration patterns and highlight the immunological vulnerability ofTP53-mutated HGSOC. pDCs appear to exert a tumor-promoting, immune-evasive role, suggesting that DC function depends on their programming and tumor context. Selective targeting of DC subsets may offer novel therapeutic opportunities inTP53-mutated, low-TMB cancers.
**背景/目的：** 本研究旨在表征三种TP53突变肿瘤类型——高级别浆液性卵巢癌、三阴性乳腺癌和子宫内膜癌——中树突状细胞的异质性、免疫关联及预后相关性，重点关注高级别浆液性卵巢癌中的浆细胞样树突状细胞。 **方法：** 分析了来自癌症基因组图谱的603例患者的RNA测序和临床数据。通过标记基因集评估了cDC祖细胞、经典树突状细胞1型、经典树突状细胞2型、浆细胞样树突状细胞和成熟树突状细胞等DC亚群的丰度。使用Kruskal-Wallis检验分析不同肿瘤间DC评分的差异。使用Kaplan-Meier法和Cox回归进行生存分析。使用Spearman相关性分析确定参数间的关联。 **结果：** 高级别浆液性卵巢癌显示出最低的pDC丰度，然而，高pDC评分与较短的无进展生存期独立相关（风险比 = 1.55，95% 置信区间：1.05–2.27；p = 0.027），这是在所有肿瘤类型中观察到的唯一与DC亚群相关的预后信号。pDC与中性粒细胞呈正相关，与单核细胞呈负相关；pDC、cDC2和cDC祖细胞与肿瘤突变负荷呈负相关。未发现pDC与TP53突变类别之间存在一致关联。然而，在已确定的热点区域内携带特定TP53突变的肿瘤表现出显著更低的pDC水平（p = 0.015）。 **结论：** 我们的研究结果揭示了TP53突变型高级别浆液性卵巢癌独特的DC浸润模式，并凸显了其免疫脆弱性。pDC似乎发挥着促进肿瘤生长和免疫逃逸的作用，这表明DC功能取决于其编程状态和肿瘤微环境。选择性靶向DC亚群可能为TP53突变、低肿瘤突变负荷的癌症提供新的治疗机会。
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