Goteri Gaia, Rupoli Serena, Campanati Anna, Costagliola Antonello, Sabato Simona, Stramazzotti Daniela, Picardi Paola, Canafoglia Lucia, Pulini Stefano, Ganzetti Giulia, Offidani Anna Maria, Leoni Pietro
Am J Transl Res. 2009 Jan 31;1(2):203-10.
Recruitment of neoplastic T cells to skin is a critical step in the pathogenesis of mycosis fungoides (MF) lesions. Cutaneous T-cell attracting chemokine (CTACK)/CCL27 attracts memory T cells to skin, resulting in increased cutaneous expression. The interactions between neoplastic cells and skin immune system require further elucidation. CTACK/CCL27 expression and density of dendritic cells (DC), CD8+ and CD4+ lymphocytes were investigated in skin lesions of 52 early-stage MF patients treated by interferon (IFN)-alpha in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA). Skin lesion biopsies obtained at diagnosis and after treatment were studied by immunohistochemistry. Initial CTACK/CCL27 expression was abnormal/suprabasal in 36 patients. Normal/basal CTACK/CCL27 expression tended to correlate with a high DC density and low CD4+ cell density in the neoplastic infiltrate. Treatment induced a significant increase in CTACK/CCL27 expression (chi(2) test: P=0.004). Overall, 33 patients relapsed [median event-free survival (EFS), 46 months] during follow-up (median, 92.5 months, range, 43-165). Normal/basal CTACK/CCL27 expression at the end of treatment correlated with lower rates of recurrence and a longer median EFS (111 months vs. 39 months with suprabasal expression; log rank test: P=0.031). CTACK/CCL27 overexpression in early-stage MF might thus be related to a balance between neoplastic cells and immunomodulant DC. Normal CTACK/CCL27 expression after treatment designates a subset of patients with favorable disease behavior. The mechanisms underpinning CTACK/CCL27 overexpression after therapy in the remaining patients, who are at greater risk of recurrence, warrant further investigation.
肿瘤性T细胞向皮肤募集是蕈样肉芽肿（MF）皮损发病机制中的关键步骤。皮肤T细胞吸引趋化因子（CTACK）/CCL27可将记忆T细胞吸引至皮肤，导致皮肤表达增加。肿瘤细胞与皮肤免疫系统之间的相互作用尚需进一步阐明。我们对52例接受α干扰素联合光化学疗法（补骨脂素加紫外线A，PUVA）治疗的早期MF患者的皮损中CTACK/CCL27的表达以及树突状细胞（DC）、CD8 +和CD4 +淋巴细胞的密度进行了研究。通过免疫组织化学对诊断时及治疗后获取的皮肤活检标本进行研究。36例患者初始CTACK/CCL27表达异常/位于基底上层。肿瘤浸润中正常/基底CTACK/CCL27表达往往与高DC密度和低CD4 +细胞密度相关。治疗使CTACK/CCL27表达显著增加（卡方检验：P = 0.004）。总体而言，33例患者在随访期间复发[无事件生存（EFS）中位数为46个月]（中位数为92.5个月，范围为43 - 165个月）。治疗结束时正常/基底CTACK/CCL27表达与较低的复发率和较长的EFS中位数相关（基底上层表达者为39个月，基底表达者为111个月；对数秩检验：P = 0.031）。因此，早期MF中CTACK/CCL27过表达可能与肿瘤细胞和免疫调节性DC之间的平衡有关。治疗后CTACK/CCL27表达正常表明一部分患者疾病行为良好。对于其余复发风险较高的患者，治疗后CTACK/CCL27过表达的潜在机制值得进一步研究。
