Yamamoto Jun, Ohuchi Kentaro, Amagai Ryo, Roh Yuna, Endo Junko, Chiba Hiromu, Tamabuchi Erika, Kambayashi Yumi, Hashimoto Akira, Asano Yoshihide, Fujimura Taku
Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan.
Skin Health Dis. 2023 Feb 12;3(3):e222. doi: 10.1002/ski2.222. eCollection 2023 Jun.
Bexarotene is often administered to phototherapy-resistant early cutaneous T-cell lymphoma (CTCL) patients as one of the first-line therapies in real-world practice. Since bexarotene reduces the expression of CCR4 in CTCL cells and CCL22 to decrease serum CCL22 levels, bexarotene inhibits the migration of CTCL cells, as well as other CCR4+ cells, such as cytotoxic T cells and regulatory T cells, in the lesional skin of CTCL. In this report, the efficacy of bexarotene in 28 cases of CTCL, as well as its correlations with immunohistochemical profiles of tumour-infiltrating leucocytes (TILs), was retrospectively investigated. The overall response rate at 1 and 4 months for the total cohort was 70.8% (95% CI, 50.6%-86.3%) and 47.8% (95% CI, 29.2%-67.0%), respectively. The disease control rate for the total cohort at 4 months was 65.2% (95% CI, 44.8%-81.3%). The mean event-free survival for all patients was 4.1 months (0.3-68.5 months). In addition, the immunoreactive cells were calculated using digital microscopy, suggesting that the ratio of CD25+ cells among TILs was significantly increased in patients who responded to bexarotene ( = 0.0209), whereas there were no significant differences in the ratios of CD8+ cells, granulysin+ cells, and Foxp3+ cells among TILs between responder and non-responder patients. Collectively, the ratio of CD25 expression among TILs might be a predictive biomarker for the efficacy of bexarotene.
在实际临床实践中,贝沙罗汀常作为一线治疗药物用于对光疗耐药的早期皮肤T细胞淋巴瘤(CTCL)患者。由于贝沙罗汀可降低CTCL细胞中CCR4的表达以及CCL22水平,从而降低血清CCL22水平,因此它能抑制CTCL细胞以及其他CCR4+细胞(如细胞毒性T细胞和调节性T细胞)在CTCL皮损中的迁移。在本报告中,我们回顾性研究了贝沙罗汀对28例CTCL患者的疗效及其与肿瘤浸润白细胞(TILs)免疫组化特征的相关性。整个队列在1个月和4个月时的总缓解率分别为70.8%(95%CI,50.6%-86.3%)和47.8%(95%CI,29.2%-67.0%)。整个队列在4个月时的疾病控制率为65.2%(95%CI,44.8%-81.3%)。所有患者的平均无事件生存期为4.1个月(0.3-68.5个月)。此外,使用数字显微镜计算免疫反应细胞,结果表明,对贝沙罗汀有反应的患者中,TILs中CD25+细胞的比例显著增加(P=0.0209),而在有反应和无反应患者之间,TILs中CD8+细胞、颗粒溶素+细胞和Foxp3+细胞的比例没有显著差异。总体而言,TILs中CD25表达比例可能是贝沙罗汀疗效预测生物标志物。