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. K E Y WO R D Santi-PD-1 therapy, CD73, head and heck squamous cell carcinoma, macrophage, small extracellular vesicle

Tricholemmal carcinoma is an extremely rare malignancy of the skin, and its biological behavior and management is controversial. The objective of the present study was to investigate the clinicopathological characteristics and management of tricholemmal carcinoma of the head and neck region. The study analyzed 15 patients with tricholemmal carcinoma. Demographic and clinical data were collected, and features associated with the management and prognosis of tricholemmal carcinoma were analyzed. Two of the 15 patients were lost to follow-up. The results showed that, during the follow-up period, 5 of the 13 available patients succumbed to the causes of recurrence (n=3), neck lymph node metastasis (n=1) and Parkinson’s disease (n=1). No patients developed distant metastasis. The disease-free survival (DFS) and overall survival (OS) were 31.1±7.8 and 32.9±7.4 months (mean ± SE), respectively, and the DFS and OS rates were 69.2 and 61.5%, respectively. In conclusion, the biological behavior of tricholemmal carcinoma is locoregionally aggressive. The recommended management for head and neck tricholemmal carcinoma is radical resection and neck dissection, and post-operative radiotherapy may be considered for high-risk patients.

Figure 8. Photographs of CPs (letter W: CuIP-1; left arch: CuIP-3; right arch: CuIP-2; letter Y: CuClP-2; letter U: CuBrP-2): a) before, b) after being ground, and c) then being exposed to acetonitrile vapor, excited by 365 nm UV light.