CD11c+CD163+ Cells and Signal Transducer and Activator of Transcription 3 (STAT3) Expression Are Common in Melanoma Leptomeningeal Disease.
CD11c+CD163+ Cells and Signal Transducer and Activator of Transcription 3 (STAT3) Expression Are Common in Melanoma Leptomeningeal Disease.
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CD11c+CD163+细胞及信号转导和转录激活因子3（STAT3）在软脑膜黑色素瘤中的表达
DOI：
10.3389/fimmu.2021.745893
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发表时间：
2021
影响因子：
7.3
通讯作者：
Heimberger AB
中科院分区：
文献类型：
--
作者：
Najem H;Marisetty A;Horbinski C;Long J;Huse JT;Glitza Oliva IC;Ferguson SD;Kumthekar PU;Wainwright DA;Chen P;Lesniak MS;Burks JK;Heimberger AB
黑色素瘤患者的软脑膜疾病（LMD）与严重的神经系统后遗症相关，预后不良，生存期通常以周为单位。尽管靶向治疗和免疫治疗对IV期黑色素瘤有治疗益处，但LMD患者通常不会受益。深入了解LMD的肿瘤微环境（TME）可能会提供更合适的治疗选择。用七种颜色的多重染色对经历LMD手术切除的受试者（n=8）进行回顾性分析，以评价整体免疫抑制中枢-信号转导子和转录激活子3（STAT 3）的表达以及CD 3 + T细胞、CD 68+单核细胞衍生细胞、CD 163+免疫抑制巨噬细胞、和CD 11 c+细胞[潜在的树突状细胞（DC）]与黑色素瘤肿瘤标志物S100 B和DAPI联合用于细胞核鉴定。使用Akoya Vectra Polaris进行高分辨率细胞成像和定量。CD 11 c+细胞在TME中占主导地位（占总细胞的10%），沿着免疫抑制性巨噬细胞（2%）。另一个潜在的DC亚群共表达CD 11 c+和CD 163+免疫抑制标志物，经常存在（8/8份标本，8%）。偶尔会发现CD 3 + T细胞，尤其是在肿瘤间质中（p=0.039）。pSTAT 3核表达在各种免疫细胞群体中是异质的。在基质和边缘上可以看到偶尔的免疫簇相互作用。总之，LMD的TME在很大程度上缺乏CD 3 + T细胞，但富含免疫抑制和先天免疫。
Leptomeningeal disease (LMD) in melanoma patients is associated with significant neurological sequela and has a dismal outcome, with survival measured typically in weeks. Despite the therapeutic benefit of targeted therapies and immunotherapies for Stage IV melanoma, patients with LMD do not typically benefit. A deeper understanding of the tumor microenvironment (TME) of LMD may provide more appropriate therapeutic selection. A retrospective analysis of subjects who underwent surgical resection with LMD (n=8) were profiled with seven color multiplex staining to evaluate the expression of the global immune suppressive hub - the signal transducer and activator of transcription 3 (STAT3) and for the presence of CD3+ T cells, CD68+ monocyte-derived cells, CD163+ immune suppressive macrophages, and CD11c+ cells [potential dendritic cells (DCs)] in association with the melanoma tumor marker S100B and DAPI for cellular nuclear identification. High-resolution cellular imaging and quantification was conducted using the Akoya Vectra Polaris. CD11c+ cells predominate in the TME (10% of total cells), along with immunosuppressive macrophages (2%). Another potential subset of DCs co-expressing CD11c+ and the CD163+ immunosuppressive marker is frequently present (8/8 of specimens, 8%). Occasional CD3+ T cells are identified, especially in the stroma of the tumor (p=0.039). pSTAT3 nuclear expression is heterogeneous in the various immune cell populations. Occasional immune cluster interactions can be seen in the stroma and on the edge. In conclusion, the TME of LMD is largely devoid of CD3+ T cells but is enriched in immune suppression and innate immunity.
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影响因子：
5.2
作者：
Tétu P;Sirven-Villaros L;Cuzzubbo S;Ursu R;Baroudjian B;Delyon J;Nataf F;De Margerie-Mellon C;Allayous C;Lefevre W;Carpentier AF;Lebbé C
通讯作者：
Lebbé C
影响因子：
3.8
作者：
Mok S;Tsoi J;Koya RC;Hu-Lieskovan S;West BL;Bollag G;Graeber TG;Ribas A
通讯作者：
Ribas A
DOI：
10.1016/s1470-2045(16)30053-5
发表时间：
2016-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Goldberg SB;Gettinger SN;Mahajan A;Chiang AC;Herbst RS;Sznol M;Tsiouris AJ;Cohen J;Vortmeyer A;Jilaveanu L;Yu J;Hegde U;Speaker S;Madura M;Ralabate A;Rivera A;Rowen E;Gerrish H;Yao X;Chiang V;Kluger HM
通讯作者：
Kluger HM
DOI：
10.1016/j.bbrc.2004.07.039
发表时间：
2004-09-03
影响因子：
3.1
作者：
Lin, T;Bost, KL
通讯作者：
Bost, KL
影响因子：
11.4
作者：
O'Farrell, AM;Liu, Y;Mui, ALF
通讯作者：
Mui, ALF