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:The impact of MITF expression on tumor-infiltrating lymphocytes in melanoma: Insights into immune microenvironment dynamics.
The impact of MITF expression on tumor-infiltrating lymphocytes in melanoma: Insights into immune microenvironment dynamics.
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黑色素瘤的进展受到肿瘤细胞与免疫微环境之间复杂相互作用的影响。本研究采用基于传统BRISK分类的改良TIL(肿瘤浸润淋巴细胞)(TILs)分类方法,探讨了原发性黑色素瘤中小眼畸形相关转录因子(MITF)表达与免疫微环境之间的关系。通过组织微阵列免疫组化分析了81例原发性黑色素瘤患者的档案福尔马林固定、石蜡包埋组织样本,以评估MITF蛋白水平。TIL模式被分为六组,对传统BRISK分类进行细化,以区分连续性与非连续性浸润,以及外周与瘤内分布。分析显示,归为BRISK B类的黑色素瘤表现出最高的MITF表达,常超过50%。相比之下,NON-BRISK和ABSENT TIL组的肿瘤显示MITF表达显著较低(均值分别为32.73% 16.98%和22.00% 10.54%),差异具有统计学意义(Kruskal-Wallis检验,P = 0.027;改良分类,P = 0.011)。
此外,CD20+ B淋巴细胞的存在与MITF表达升高相关(P = 0.009)。29%的病例检测到MITF基因扩增,但其与蛋白表达的关联仅显示出趋势(P = 0.058)。这些发现凸显了黑色素瘤中MITF表达与TIL分布之间复杂的相互作用,提示细化的TIL分类可能为肿瘤免疫生物学提供更深入的见解,并有助于预测免疫治疗的反应。
Melanoma progression is influenced by complex interactions between tumor cells and the immune microenvironment.
This study examined the relationship between microphthalmia-associated transcription factor (MITF) expression and the immune microenvironment in primary melanoma using a modified classification of tumor-infiltrating lymphocytes (TILs) based on conventional BRISK categories. Archival formalin-fixed, paraffin-embedded tissue samples from 81 primary melanoma patients were analyzed via tissue microarray immunohistochemistry to assess MITF protein levels.
TIL patterns were categorized into six groups, refining the traditional BRISK classification to distinguish between continuous and discontinuous infiltration, as well as peripheral vs intratumoral distribution. The analysis revealed that melanomas classified under the BRISK B category exhibited the highest MITF expression, often exceeding 50%.
In contrast, tumors in the NON-BRISK and ABSENT TIL groups showed significantly lower MITF expression (mean values: 32. 73% 16. 98% and 22. 00% 10. 54%, respectively), with statistically significant differences (Kruskal-Wallis test, P = 0. 027; modified classification, P = 0. 011).
Additionally, the presence of CD20+ B lymphocytes correlated with increased MITF expression (P = 0. 009). MITF gene amplification was detected in 29% of cases, though its association with protein expression showed only a trend (P = 0. 058).
These findings highlight the complex interplay between MITF expression and TIL distribution in melanoma, suggesting that refined TIL classification may offer deeper insights into tumor immunobiology and help predict responses to immunotherapy.
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