Triggering Receptor Expressed on Myeloid Cells in Cutaneous Melanoma.
Triggering Receptor Expressed on Myeloid Cells in Cutaneous Melanoma.
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DOI：
10.1111/cts.12308
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发表时间：
2015-10
期刊：
影响因子：
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通讯作者：
Agrawal DK
中科院分区：
文献类型：
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作者：
Nguyen AH;Koenck C;Quirk SK;Lim VM;Mitkov MV;Trowbridge RM;Hunter WJ 3rd;Agrawal DK
肿瘤微环境在黑色素瘤的发展过程中起着重要作用，黑色素瘤是典型的免疫性皮肤恶性肿瘤。髓系细胞上表达的触发受体(TREM)家族的先天免疫受体调节炎症和先天免疫信号。它已经在各种肿瘤疾病中被研究过，但在黑色素瘤中还没有。本研究检测了人皮肤黑色素瘤及其周围组织中TREM-1(促炎增强剂)和TREM-2(抗炎调节剂和吞噬促进剂)的表达。对10例黑色素瘤患者的皮肤活检标本进行间接免疫荧光染色，并对染色强度进行半定量评分。TREM-1和TREM-2在角质形成细胞中的表达高于黑色素瘤组织(TREM-1：P<；0.01；TREM-2：P<；0.01)。TREM-2在正常角质形成细胞中主要表达，而TREM-1在黑色素瘤组织中主要表达(TREM-1与TREM-2比值：角质形成细胞=0.78；黑色素瘤=2.08；P<；0.01)。黑色素瘤组织中TREM比率的增加可能会导致微环境的促炎和促肿瘤状态。这一证据可能暗示了TREM-1/TREM-2范式，在该范式中，相对水平决定了炎症和免疫状态，而不是其中之一的绝对表达。关于这一范例的进一步研究是有必要的，并可能在黑色素瘤的治疗中具有预后或治疗价值。
The tumor microenvironment plays an important role in the progression of melanoma, the prototypical immunologic cutaneous malignancy. The triggering receptor expressed on myeloid cells (TREM) family of innate immune receptors modulates inflammatory and innate immune signaling. It has been investigated in various neoplastic diseases, but not in melanoma. This study examines the expression of TREM-1 (a pro-inflammatory amplifier) and TREM-2 (an anti-inflammatory modulator and phagocytic promoter) in human cutaneous melanoma and surrounding tissue. Indirect immunofluorescence staining was performed on skin biopsies from 10 melanoma patients and staining intensity was semi-quantitatively scored. Expression of TREM-1 and TREM-2 was higher in keratinocytes than melanoma tissue (TREM-1: p < 0.01; TREM-2: p < 0.01). Whereas TREM-2 was the dominant isoform expressed in normal keratinocytes, TREM-1 expression predominated in melanoma tissue (TREM-1 to TREM-2 ratio: keratinocytes = 0.78; melanoma = 2.08; p <0.01). The increased TREM ratio in melanoma tissue could give rise to a pro-inflammatory and pro-tumor state of the microenvironment. This evidence may be suggestive of a TREM-1/TREM-2 paradigm in which relative levels dictate inflammatory and immune states, rather than absolute expression of one or the other. Further investigation regarding this paradigm is warranted and could carry prognostic or therapeutic value in treatment for melanoma.