免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Association of BRAF Mutation Status with Histopathological Characteristics and Survival Outcomes in Stage II-III Malignant Melanoma.
Association of BRAF Mutation Status with Histopathological Characteristics and Survival Outcomes in Stage II-III Malignant Melanoma.
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在晚期或转移性黑色素瘤患者中,常规进行BRAF突变评估以识别可能从BRAF靶向治疗中获益的患者。本研究旨在评估BRAF突变状态与II期和III期恶性黑色素瘤患者组织病理学特征及生存之间的关系。分析纳入了一个前瞻性队列,包括在一家综合癌症中心接受治疗的108例pT3恶性黑色素瘤患者。所有患者在2016年至2024年间均按照当代黑色素瘤管理指南接受治疗,最短随访时间为12个月,延长至2025年。在研究队列中进行了总生存期(OS)和无进展生存期(PFS)分析。
该研究纳入108例II-III期恶性黑色素瘤患者,平均年龄为56.73 13.51岁。浅表扩散性黑色素瘤是最常见的组织学亚型,其次是结节性和肢端黑色素瘤。大多数肿瘤被分类为Clark IV级,中位Breslow厚度为3 mm,且大多数病例存在溃疡。超过半数患者观察到淋巴结受累,56.48%的病例发现BRAF突变(最常见的变异为V600E)。与BRAF突变型肿瘤相比,BRAF野生型肿瘤中活跃的TIL(肿瘤浸润淋巴细胞)显著更常见。在评估与生存的关联时,未发现BRAF突变状态是独立预测因子。在多变量Cox模型中,TIL状态与改善的OS相关(HR 3.33,95% CI 1.41-7.88,p = 0.006)。
此外,在多变量分析中,TIL状态也与改善的PFS相关(HR 5.23,95% CI 2.22-12.3,p < 0.001)。BRAF野生型肿瘤显著更可能出现活跃的浸润。未发现BRAF突变状态是生存的独立预测因素。在多变量分析中,TIL状态仍与OS和PFS显著相关。
In patients with advanced or metastatic melanoma, BRAF mutation assessment is routinely performed to identify patients who may benefit from BRAF-targeted therapy.
This study aimed to assess the role of BRAF mutation status in relation to histopathological characteristics and survival of patients with stage II and III malignant melanoma. A prospective cohort of 108 patients with pT3 malignant melanoma who were treated in a comprehensive cancer center were included in the analysis. All patients were treated according to contemporary melanoma management guidelines between 2016 and 2024, with a minimum follow-up of 12 months extending to 2025.
Overall survival (OS) and progression-free survival (PFS) analyses were performed in the study cohort. The study included 108 patients with stage II-III malignant melanoma, with a mean age of 56. 73 13. 51 years. Superficial spreading melanoma was the most frequent histological subtype, followed by nodular and acral melanoma. Most tumors were classified as Clark level IV, with a median Breslow thickness of 3 mm, and ulceration was present in the majority of cases.
Lymph node involvement was observed in over half of the patients, and BRAF mutations were identified in 56. 48% of cases (the most common variant was V600E). Brisk tumor-infiltrating lymphocytes were significantly more frequent in BRAF wild-type tumors compared with BRAF-mutant tumors. When assessing associations with survival, BRAF mutation status was not found to be an independent predictor. In the multivariate Cox model, TIL status was associated with improved OS (HR 3. 33, 95% CI 1. 41-7. 88, p = 0. 006).
In addition, in the multivariate analysis, TIL status was also associated with improved PFS (HR 5. 23, 95% CI 2. 22-12. 3, p < 0. 001). BRAF wild-type tumors were significantly more likely to exhibit a brisk infiltrate. BRAF mutation status was not found to be an independent predictor of survival. TIL status remained significantly associated with OS and PFS in multivariable analysis.
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