Exosomal PD-L1 derived from head and neck squamous cell carcinoma promotes immune evasion by activating the positive feedback loop of activated regulatory T cell-M2 macrophage.

The positive feedback loop of activated regulatory T cells (aTregs) and M2 macrophages (M2) play a vital role in promoting the tumor immunosuppressive microenvironment of head and neck squamous cell carcinoma (HNSCC). However, the key factors regulating the positive feedback loop remain unclear. Herein, we investigated the effect of PD-L1 carried on exosomes derived from tumor cells (TEXs) on the aTreg-M2 positive feedback loop, as well as their role in mediating immunosuppression. In our study, TEXs with or without PD-L1 (TEX-PD-L1 or TEX-PD-L1KO) were treated with CD4+CD25- T cells and M0 macrophages, and the effect on the differentiation of aTregs, M2 and the aTreg-M2 positive feedback loop was assessed. TEXs carried more PD-L1 than tumor cells and not only promoted the differentiation of aTregs and M2, but also, most importantly, enhanced the positive feedback loop of aTreg-M2, which inhibited the proliferation of CD4+CD25- T cells and in turn led to tumor immune escape. Moreover, in vivo study showed that TEX-PD-L1KO could inhibit tumor growth and significantly improve the antitumor efficacy in both the peripheral and tumor microenvironments. Collectively this study revealed the role and mechanism of TEX-PD-L1 in negative immune regulation, and targeting TEX-PD-L1 may be a new idea and strategy for immunotherapy of HNSCC.

The survival benefit of lymph node dissection in resected T1-2, cN0 supraglottic cancer: A population-based propensity score matching analysis.

BACKGROUND: The survival benefit of clinically negative cervical lymph nodes (cN0) in patients with T1-2 supraglottic cancer (SC) remains unclear. This study aimed to comprehensively evaluate the prognostic value of lymph node dissection (LND) in patients with T1-2, cN0 SC. METHODS: We included 1036 confirmed T1-2, cN0 SC patients with clinicopathological characteristics between 2004 and 2015, based on the Surveillance, Epidemiology, and End Results program (SEER) database. The association between LND and overall survival (OS) was investigated by the Kaplan-Meier method. RESULTS: Before propensity score matching (PSM), patients selected for LND had better OS, compared to patients did not receive LND (5-year OS: 62.6% vs 51.2%, respectively; p = 0.011). After PSM, the LND group also present significant improvement in prognosis (5-year OS: 64.3% vs 51.7%, respectively; p < 0.01). CONCLUSIONS: LND was significantly associated with a more favorable prognosis compared with non-LND in patients with T1-2, cN0 SC.