Plasmacytoid Dendritic Cell (pDC) Infiltration Correlate with Tumor Infiltrating Lymphocytes, Cancer Immunity, and Better Survival in Triple Negative Breast Cancer (TNBC) More Strongly than Conventional Dendritic Cell (cDC).
Plasmacytoid Dendritic Cell (pDC) Infiltration Correlate with Tumor Infiltrating Lymphocytes, Cancer Immunity, and Better Survival in Triple Negative Breast Cancer (TNBC) More Strongly than Conventional Dendritic Cell (cDC).
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DOI：
10.3390/cancers12113342
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发表时间：
2020-11-12
期刊：
影响因子：
5.2
通讯作者：
Takabe K
中科院分区：
文献类型：
--
作者：
Oshi M;Newman S;Tokumaru Y;Yan L;Matsuyama R;Kalinski P;Endo I;Takabe K
树突状细胞（DC）是肿瘤免疫微环境（TIME）中的主要抗原呈递细胞，在肿瘤免疫中起着重要作用。使用转录组学分析在大的患者队列中研究浆细胞样DC（pDC）和常规DC（cDC）浸润的临床相关性。我们发现高pDC与三阴性乳腺癌（TNBC）的更好生存率显著相关，但与cDC无关。高pDC TNBC肿瘤比cDC TNBC更强地富集免疫和炎症相关基因集，包括IFN-γ信号传导，cDC TNBC也富集转移相关基因集。pDC与CD 8+和CD 4+记忆T细胞相关，并且在TNBC中具有比cDC更强的细胞溶解活性评分。高pDC TNBC与高比例的抗癌免疫细胞和所检查的所有免疫检查点分子的高表达相关。我们首次发现pDC与TNBC患者的免疫应答和存活率的相关性比cDC更强。树突状细胞（DC）是肿瘤免疫微环境（TIME）中的主要抗原呈递细胞类型，在肿瘤免疫中起重要作用。常规DC（cDC）和浆细胞样DC（pDC）通过xCell算法定义，共分析了2968例乳腺癌患者（TCGA和METABRIC）。我们发现，与其他亚型相比，三阴性乳腺癌（TNBC）具有高比例的cDC和pDC。与cDC相反，TNBC中的高pDC与两个队列中一致的更好的疾病特异性和无疾病生存期显著相关。在基因集富集分析中，高cDC TNBC肿瘤不仅富集炎症和免疫相关的基因集，而且还富集转移相关的基因集，而高pDC TNBC比cDC更强地富集炎症和免疫相关的基因集，包括IFN-γ信号传导。pDC TNBC与CD 8+、CD 4+记忆、IFN-γ评分和溶细胞活性的相关性强于cDC TNBC。高pDC TNBC与高比例的抗癌免疫细胞和所有检查的免疫检查点分子的高表达相关。总之，与cDC相比，pDC水平与TNBC中免疫细胞浸润和患者存活率的相关性更强;这是第一项表明TNBC中pDC浸润的临床相关性的研究。
Dendritic cells (DC) represent a major antigen-presenting cell in the tumor immune microenvironment (TIME) and play an essential role in cancer immunity. Clinical relevance of plasmacytoid DC (pDC) and conventional DC (cDC) infiltration were studied in large patient cohorts using transcriptomic analyses. We found that high pDC was significantly associated with better survival in triple negative breast cancer (TNBC), but not cDC. High pDC TNBC tumors enriched immune and inflammation-related gene sets including IFN-γ signaling more strongly than cDC TNBC, which also enriched metastasis-related gene sets. pDC correlated with CD8+ and CD4+ memory T cells, and had a cytolytic activity score stronger than cDC in TNBC. High pDC TNBC were associated with a high fraction of anti-cancer immune cells and high expression of all the immune checkpoint molecules examined. For the first time, we found that pDC are correlated with immune response and survival in TNBC patients more strongly than cDC. Dendritic cells (DC) represent a major antigen-presenting cell type in the tumor immune microenvironment (TIME) and play an essential role in cancer immunity. Conventional DC (cDC) and plasmacytoid DC (pDC) were defined by the xCell algorithm and a total of 2968 breast cancer patients (TCGA and METABRIC) were analyzed. We found that triple-negative breast cancer (TNBC) had a high fraction of cDC and pDC compared to the other subtypes. In contrast to cDC, high pDC in TNBC was significantly associated with better disease-specific and disease-free survival consistently in both cohorts. High cDC TNBC tumors enriched not only inflammation and immune-related, but also metastasis-related gene sets in Gene Set Enrichment Analysis, whereas high pDC TNBC enriched inflammation and immune -related gene sets including IFN-γ signaling more strongly than cDC. pDC TNBC correlated with CD8+, CD4+ memory, IFN-γ score, and cytolytic activity stronger than cDC TNBC. High pDC TNBC were associated with a high fraction of anti-cancer immune cells and high expression of all the immune check point molecules examined. In conclusion, pDC levels correlated with the infiltration of immune cells and patient survival in TNBC more strongly than cDC; this is the first study suggesting the clinical relevance of pDC infiltration in TNBC.
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影响因子：
45.3
作者：
Adams, Sylvia;Gray, Robert J.;Badve, Sunil S.
通讯作者：
Badve, Sunil S.
影响因子：
64.5
作者：
Liu J;Lichtenberg T;Hoadley KA;Poisson LM;Lazar AJ;Cherniack AD;Kovatich AJ;Benz CC;Levine DA;Lee AV;Omberg L;Wolf DM;Shriver CD;Thorsson V;Cancer Genome Atlas Research Network;Hu H
通讯作者：
Hu H
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
11.2
作者：
Li T;Fan J;Wang B;Traugh N;Chen Q;Liu JS;Li B;Liu XS
通讯作者：
Liu XS
头颈鳞状细胞癌中选择性剪接景观的综合表征揭示了与肿瘤发生和免疫微环境相关的新事件。
影响因子：
12.4
作者：
Li, Zhi-Xuan;Zheng, Zi-Qi;Sun, Ying
通讯作者：
Sun, Ying