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
黑色素瘤瘤内 PTEN 异质性的多平台分析
英文原题：Multiplatform Analysis of Intratumoral PTEN Heterogeneity in Melanoma.
查看英文原题
Multiplatform Analysis of Intratumoral PTEN Heterogeneity in Melanoma.
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中文摘要
肿瘤抑制因子PTEN蛋白表达的缺失与黑色素瘤侵袭性增加、肿瘤免疫浸润减少以及对免疫治疗和靶向治疗的耐药性相关。我们评估了一个独特的队列，包含八个PTEN蛋白表达局灶性缺失的黑色素瘤样本，以了解该疾病中PTEN缺失的特征和机制。
我们使用DNA测序、DNA甲基化、RNA表达、数字空间分析和免疫组化平台，将PTEN阴性（PTEN[-]）区域与其相邻的PTEN阳性（PTEN[+]）区域进行了比较。在三个病例（37.5%）中，PTEN(-)区域发现了PTEN的变异或纯合缺失，而相邻的PTEN(+)区域未检测到这些改变，但在其余PTEN(-)样本中未发现明确的基因组或DNA甲基化缺失基础。来自两个独立平台的RNA表达数据一致发现，与相邻PTEN(+)区域相比，PTEN(-)区域的染色体分离基因表达增加。蛋白质组学分析显示，与相邻PTEN(+)区域相比，PTEN(-)区域中TIL（肿瘤浸润淋巴细胞）相对稀少。这些发现增进了我们对黑色素瘤潜在瘤内分子异质性以及该疾病中与PTEN蛋白缺失相关特征的理解。
展开英文摘要原文
Loss of protein expression of the tumor suppressor PTEN is associated with increased cancer aggressiveness, decreased tumor immune infiltration, and resistance to immune and targeted therapies in melanoma.
We assessed a unique cohort of eight melanoma samples with focal loss of PTEN protein expression to understand the features and mechanisms of PTEN loss in this disease.
We compared the PTEN-negative (PTEN[-]) areas to their adjacent PTEN-positive (PTEN[+]) areas using DNA sequencing, DNA methylation, RNA expression, digital spatial profiling, and immunohistochemical platforms. Variations or homozygous deletions of PTEN were identified in PTEN(-) areas that were not detected in the adjacent PTEN(+) areas in three cases (37. 5%), but no clear genomic or DNA methylation basis for loss was identified in the remaining PTEN(-) samples.
RNA expression data from two independent platforms identified a consistent increase in chromosome segregation gene expression in PTEN(-) versus adjacent PTEN(+) areas. Proteomic analysis showed a relative paucity of tumor-infiltrating lymphocytes in PTEN(-) versus adjacent PTEN(+) areas. The findings add to our understanding of potential molecular intratumoral heterogeneity in melanoma and the features associated with the loss of PTEN protein in this disease.
论文信息
- 作者
- Chagani S、De Macedo MP、Carapeto F、Wang F、Marzese DM、Wani K、Haydu LE、Peng W
- 第一作者单位
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.United States
- 通讯作者单位
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Melanoma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address: MDavies@mdanderson.org.United States
- 文献类型
- 非美国政府资助研究 · 美国 NIH 资助研究
- 期刊
- The Journal of investigative dermatology2023 Sep
- 原文标识
- PubMed 36871660 · DOI 10.1016/j.jid.2023.01.034
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