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人类瘤相关的巨细胞和中性粒细胞通过致死性和亚致死性巨细胞症来调节抗瘤抗体的有效性

Sunil Singhal¹, Abhishek S Rao¹, Jason Stadanlick¹

¹Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Cancer research

|January 25, 2024

概括

骨髓状细胞使用抗体依赖性巨细胞化 (ADT) 与瘤细胞相互作用,导致癌细胞死亡或抵抗. 了解这些机制可以改善固体瘤的抗体疗法.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
癌症研究癌症研究

背景情况:

在固体瘤中瘤向抗体 (tAbs) 的临床益处有限.
tAbs的有效性通常依赖于表达Fc受体 (FcR) 的白细胞,如瘤相关巨细胞 (TAM) 和中性粒细胞 (TAN).
了解tAb反应中的骨髓质效应机制对于提高癌症治疗疗效至关重要.

研究的目的:

为了研究骨髓效应因子与tAb-opsonized癌细胞相互作用的机制.
确定这些相互作用如何影响瘤细胞的杀死或抵抗.
确定改善tAb治疗固体瘤的策略.

主要方法:

研究了抗体依赖性细胞分裂 (ADT) 和抗体依赖性细胞分裂在髓质效应体和瘤细胞相互作用中.
分析了效应因子与瘤比率和向抗原 (tAg) 水平对ADT结果的影响.
研究了不同髓状细胞群 (TAMs,TANs,PBNs) 和抗体同型 (IgG1,IgA) 在调解抗癌作用中的作用.

主要成果:

骨髓状细胞主要利用ADT",食"具有tAb/tAg复合体的瘤细胞碎片,而不是细胞化.
只有在高tAg和效应剂与瘤比率下,ADT是瘤杀伤性的;否则,它是次致命的.
通过TAMs进行的亚致命ADT导致瘤细胞逃脱和T细胞通过交叉呈现刺激.
抗EGFR抗体IgA显示出瘤杀伤活性,并抵消了TAN介导的瘤生长促进作用,与IgG1.

结论:

与tAb治疗瘤的骨髓质效应体相互作用可以导致瘤细胞死亡或通过ADT等机制抵抗.
亚致命性ADT可以促进瘤免疫逃脱,并可能增强抗瘤T细胞反应.
抗体同型的类型 (例如,IgA与IgG1) 显著影响了髓质效应因子与癌细胞接触的结果.
阐明这些机制是开发改进的基于抗体的癌症疗法的关键.

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