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
中性粒细胞和中性粒细胞胞外诱捕网在人 NMSC 中的证据及其与临床危险因素、溃疡和 CD8(+) T 细胞浸润的关系
英文原题：Evidence of Neutrophils and Neutrophil Extracellular Traps in Human NMSC with Regard to Clinical Risk Factors, Ulceration and CD8(+) T Cell Infiltrate.
查看英文原题
Evidence of Neutrophils and Neutrophil Extracellular Traps in Human NMSC with Regard to Clinical Risk Factors, Ulceration and CD8(+) T Cell Infiltrate.
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中文摘要
非黑色素瘤皮肤癌（NMSC），包括基底细胞癌（BCC）、皮肤鳞状细胞癌（cSCC）和梅克尔细胞癌（MCC），日益常见并带来显著的医疗挑战。中性粒细胞胞外诱捕网（NETs），即中性粒细胞排出的染色质纤维，可通过损害 CD8+ T 细胞介导的细胞毒性促进免疫治疗耐药。
在此，为确定潜在治疗靶点，我们研究 NMSC 中 NETs 的排出及其与 CD8+ T 细胞浸润的关系。对中性粒细胞（CD15）和 NETs（H3cit）进行免疫荧光染色，以及对细胞毒性 T 细胞（CD8+）进行免疫组化染色，在人类 cSCC（n = 24）、BCC（n = 17）和 MCC（n = 12）中，显示中性粒细胞浸润与 BCC 和 MCC 中的溃疡直径相关，但与 cSCC 无关。在 BCC 和 cSCC 中，中性粒细胞浸润也与横截面积（CSA）相关。NETs 与已确立的风险因素无关，但与溃疡的存在相关，并且在 cSCC 中与脓肿样结构相关。在 NET 阳性的肿瘤中，或在中性粒细胞浸润更密集的肿瘤中，CD8+ T 细胞浸润并未减少。
本研究首次报道并描述了 NMSC 中的 NETs。因此，它为这一相关但研究不足的主题提供了进一步研究的动力。
展开英文摘要原文
Non-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), are increasingly common and present significant healthcare challenges. Neutrophil extracellular traps (NETs), chromatin fibers expulsed by neutrophil granulocytes, can promote immunotherapy resistance via an impairment of CD8 + T cell-mediated cytotoxicity.
Here, to identify a potential therapeutic target, we investigate the expulsion of NETs and their relation to CD8 + T cell infiltration in NMSC. Immunofluorescence staining for neutrophils (CD15) and NETs (H3cit), as well as immunohistochemistry for cytotoxic T cells (CD8 + ) on human cSCCs ( n = 24), BCCs ( n = 17) and MCCs ( n = 12), revealed a correlation between neutrophil infiltration and ulceration diameter in BCC and MCC, but not in cSCC.
In BCC and cSCC, neutrophil infiltration also correlated with the cross-sectional area (CSA). NETs were not associated with established risk factors but with the presence of an ulceration, and, in cSCC, with abscess-like structures. CD8 + T cell infiltration was not reduced in tumors that were NET-positive nor in those with a denser neutrophil infiltration.
This study is the first to report and characterize NETs in NMSC.
Thus, it gives an incentive for further research in this relevant yet understudied topic.
论文信息
- 作者
- Moeller LH、Weishaupt C、Schedel F
- 单位
- Department of Dermatology, Skin Cancer Center, University Clinic Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany.Germany
- 期刊
- International journal of molecular sciences2024 Oct 2
- 原文标识
- PubMed 39408949 · DOI 10.3390/ijms251910620
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