CD73 in small extracellular vesicles derived from HNSCC defines tumour-associated immunosuppression mediated by macrophages in the microenvironment.
CD73 in small extracellular vesicles derived from HNSCC defines tumour-associated immunosuppression mediated by macrophages in the microenvironment.
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DOI：
10.1002/jev2.12218
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发表时间：
2022-05
影响因子：
16
通讯作者：
中科院分区：
文献类型：
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对肿瘤细胞源性小细胞外囊泡（sEV）调节肿瘤微环境（TME）的研究为头颈部鳞状细胞癌（HNSCC）的靶向治疗提供了策略。在此，我们证明来源于HNSCC癌细胞的sEV携带CD 73（sEVsCD 73），其促进恶性进展并介导免疫逃避。在TME中被肿瘤相关巨噬细胞（TAM）吞噬的sEVsCD 73诱导免疫抑制。HNSCC微环境中较高的CD 73高TAM浸润水平与较差的预后相关，而sEVsCD 73激活TAM中的NF-κB通路，从而通过增加细胞因子分泌（如IL-6、IL-10、TNF-α和TGF-β1）抑制免疫功能。sEVsCD 73的缺乏通过逆转免疫抑制增强了抗PD-1治疗的敏感性。此外，循环sEVsCD 73增加了淋巴结转移和预后不良的风险。总之，我们的研究表明，来源于肿瘤细胞的sEVsCD 73有助于免疫抑制，并且是HNSCC中免疫检查点治疗的抗PD-1应答的潜在预测因子。
Research on tumour cell‐derived small extracellular vesicles (sEVs) that regulate tumour microenvironment (TME) has provided strategies for targeted therapy of head and neck squamous cell carcinoma (HNSCC). Herein, we demonstrated that sEVs derived from HNSCC cancer cells carried CD73 (sEVsCD73), which promoted malignant progression and mediated immune evasion. The sEVsCD73 phagocytosed by tumour‐associated macrophages (TAMs) in the TME induced immunosuppression. Higher CD73high TAMs infiltration levels in the HNSCC microenvironment were correlated with poorer prognosis, while sEVsCD73 activated the NF‐κB pathway in TAMs, thereby inhibiting immune function by increasing cytokines secretion such as IL‐6, IL‐10, TNF‐α, and TGF‐β1. The absence of sEVsCD73 enhanced the sensitivity of anti‐PD‐1 therapy through reversed immunosuppression. Moreover, circulating sEVsCD73 increased the risk of lymph node metastasis and worse prognosis. Taken together, our study suggests that sEVsCD73 derived from tumour cells contributes to immunosuppression and is a potential predictor of anti‐PD‐1 responses for immune checkpoint therapy in HNSCC.
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影响因子：
16
作者：
Kang M;Jordan V;Blenkiron C;Chamley LW
通讯作者：
Chamley LW
影响因子：
16
作者：
Henrich SE;McMahon KM;Plebanek MP;Calvert AE;Feliciano TJ;Parrish S;Tavora F;Mega A;De Souza A;Carneiro BA;Thaxton CS
通讯作者：
Thaxton CS
影响因子：
50.3
作者：
Lee, Heng-Huan;Wang, Ying-Nai;Hung, Mien-Chie
通讯作者：
Hung, Mien-Chie
影响因子：
64.5
作者：
Hugo W;Zaretsky JM;Sun L;Song C;Moreno BH;Hu-Lieskovan S;Berent-Maoz B;Pang J;Chmielowski B;Cherry G;Seja E;Lomeli S;Kong X;Kelley MC;Sosman JA;Johnson DB;Ribas A;Lo RS
通讯作者：
Lo RS
影响因子：
16.6
作者：
Brown MC;Mosaheb MM;Mohme M;McKay ZP;Holl EK;Kastan JP;Yang Y;Beasley GM;Hwang ES;Ashley DM;Bigner DD;Nair SK;Gromeier M
通讯作者：
Gromeier M