Open AccessCD73 in small extracellular vesicles derived from HNSCC defines tumour‐associated immunosuppression mediated by macrophages in the microenvironment
Author(s) -
Lu Tingwei,
Zhang Zhen,
Zhang Jianjun,
Pan Xinhua,
Zhu Xueqin,
Wang Xu,
Li Zhihui,
Ruan Min,
Li Huasheng,
Chen Wantao,
Yan Ming
Publication year - 2022
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1002/jev2.12218
Subject(s) - tumor microenvironment , immunosuppression , immune system , cancer research , head and neck squamous cell carcinoma , lymph node , medicine , immunology , biology , cancer , head and neck cancer
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 (sEVs CD73 ), which promoted malignant progression and mediated immune evasion. The sEVs CD73 phagocytosed by tumour‐associated macrophages (TAMs) in the TME induced immunosuppression. Higher CD73 high TAMs infiltration levels in the HNSCC microenvironment were correlated with poorer prognosis, while sEVs CD73 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 sEVs CD73 enhanced the sensitivity of anti‐PD‐1 therapy through reversed immunosuppression. Moreover, circulating sEVs CD73 increased the risk of lymph node metastasis and worse prognosis. Taken together, our study suggests that sEVs CD73 derived from tumour cells contributes to immunosuppression and is a potential predictor of anti‐PD‐1 responses for immune checkpoint therapy in HNSCC.