Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma.
Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma.
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DOI：
10.1158/0008-5472.can-11-3218
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发表时间：
2012-03-01
期刊：
影响因子：
11.2
通讯作者：
Slingluff CL Jr
中科院分区：
文献类型：
--
作者：
Erdag G;Schaefer JT;Smolkin ME;Deacon DH;Shea SM;Dengel LT;Patterson JW;Slingluff CL Jr
浸润黑色素瘤转移微环境的免疫细胞可能限制或促进肿瘤进展，但区分这些作用的特征尚不清楚。在这项研究中，我们系统地评估了浸润人类患者黑色素瘤转移的免疫细胞的组成和组织。免疫细胞浸润的三种组织学模式被鉴定，命名为免疫型A、B和C。免疫型A的特征在于没有免疫细胞浸润。免疫型B的特征在于仅限于肿瘤内血管近端区域的免疫细胞浸润。免疫型C的特征在于弥漫性免疫细胞浸润整个转移性肿瘤。这些免疫型分别占转移灶的29%、63%和8%，估计中位生存期分别为15、23和130个月。值得注意的是，所有三种免疫型均显示B细胞比例增加，巨噬细胞比例降低。总的来说，主要的免疫细胞是T细胞（53%）、B细胞谱系细胞（33%）和巨噬细胞（13%），NK细胞和成熟树突状细胞很少存在。虽然较高密度的CD 8 + T细胞与存活率相关性最好，但较高密度的CD 45+白细胞、T细胞和B细胞也与存活率增加相关。总之，我们的研究结果揭示了患者黑色素瘤转移中免疫浸润的显著差异，表明影响免疫细胞募集的免疫归巢受体和配体的微环境差异。这些发现很重要，不仅揭示了免疫微环境如何影响结果，而且还揭示了可能有助于改善转移性黑色素瘤患者个体化治疗的特征。
Immune cells infiltrating the microenvironment of melanoma metastases may either limit or promote tumor progression, but the characteristics that distinguish these effects are obscure. In this study, we systematically evaluated the composition and organization of immune cells that infiltrated melanoma metastases in human patients. Three histologic patterns of immune cell infiltration were identified, designated immunotypes A, B and C. Immunotype A was characterized by no immune cell infiltrate. Immunotype B was characterized by infiltration of immune cells limited only to regions proximal to intratumoral blood vessels. Immunotype C was characterized by a diffuse immune cell infiltrate throughout a metastatic tumor. These immunotypes represented 29%, 63%, and 8% of metastases with estimated median survival periods of 15, 23, and 130 months, respectively. Notably, all three immunotypes showed increasing proportions of B cells and decreasing proportions of macrophages. Overall, the predominant immune cells were T cells (53%), B cell lineage cells (33%), and macrophages (13%), with NK and mature dendritic cells only rarely present. While higher densities of CD8+ T cells correlated best with survival, a higher density of CD45+ leukocytes, T cells, and B cells also correlated with increased survival. Together, our findings reveal striking differences in the immune infiltrate in melanoma metastases in patients, suggesting microenvironmental differences in immune homing receptors and ligands that affect immune cell recruitment. These findings are important, not only by revealing how the immune microenvironment can affect outcomes but also because they reveal characteristics that may help improve individualized therapy for patients with metastatic melanoma.