The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation
Dan Yu,Xueshibojie Liu,Guang‐Hong Han,Yan Liu,Xue Zhao,Di Wang,Xiaomin Bian,Tingting Gu,Lianji Wen +8 more
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TLDR
Targeting let-7 family of microRNAs as candidates that up-regulate tumor cell PD-L1 expression and mediates immune evasion of head and neck squamous cell carcinoma (HNSCC) is highlighted as a potential strategy to enhance immune checkpoint therapy for HNSCC.Abstract:
Accumulation of immunosuppressive protein programmed death-ligand 1 (PD-L1) has been documented in several cancers and contributes to the evasion of the host immune system. However, cancer cell-intrinsic signaling-dependent control of PD-L1 expression remains to be elucidated. Herein, we aimed to identify the let-7 family of microRNAs as candidates that up-regulate tumor cell PD-L1 expression and mediates immune evasion of head and neck squamous cell carcinoma (HNSCC). The expression of let-7 family and PD-L1 was quantified in HNSCC tissues and adjacent normal tissues. PD-L1 degradation was evaluated in HNSCC cells in response to elevated expressions of let-7a or let-7b. The regulation of let-7 family on PD-L1 degradation through a mechanism involving T-cell factor-4 (TCF-4) control of β-catenin/STT3 pathway was evaluated. Immune recognition of HNSCC in vivo was examined in subcutaneous tumor-bearing C3H mice in the presence of let-7a/b and/or CTLA-4 antibody. The let-7 family were significantly down-regulated in the context of HNSCC, sharing a negative correlation with PD-L1 expression. Glycosylated PD-L1 was detected in HNSCC cells, which was reduced by let-7a/b over-expression. TCF-4, the target of let-7a/b, activated the β-catenin/STT3 pathway and promoted PD-L1 degradation. In vivo analysis demonstrated that let-7a/b over-expression potentiated anticancer immunotherapy by CTLA-4 blockade. Taken together, our findings highlight targeting let-7 family as a potential strategy to enhance immune checkpoint therapy for HNSCC.read more
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Mutational drivers of cancer cell migration and invasion.
TL;DR: This review summarises data from published literature on the effect of chromosomal instability and genetic mutations on cancer cell migration and invasion and suggests a role for genetic alterations in invasion is not universally accepted.
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The effects of checkpoint inhibition on head and neck squamous cell carcinoma: A systematic review.
TL;DR: There is a further need for randomized clinical trials investigating a putative role of checkpoint inhibition in the treatment of advanced HNSCC.
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Characteristics and impact of programmed death-ligand 1 expression, CD8+ tumor-infiltrating lymphocytes, and p16 status in head and neck squamous cell carcinoma
Nuttapong Ngamphaiboon,Teeranuch Chureemas,Teerada Siripoon,Lalida Arsa,N. Trachu,Chuleeporn Jiarpinitnun,P. Pattaranutaporn,Ekaphop Sirachainan,Noppadol Larbcharoensub +8 more
TL;DR: A high prevalence of PD-L1 expression was observed in HNSCC and was associated with older age, while highly PD- L1 expression (≥ 50%) was an independent prognostic factor for poor OS in anti-PD1/PD-L 1 untreated HNS CC patients.
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The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness
TL;DR: The role of the let-7 family of microRNAs in regulating cancer stemness was reviewed in this article, where several key RNA-binding proteins, including long non-coding RNAs (lncRNAs) and circular RNAs, were discussed.
Journal ArticleDOI
miRNAs as potential game-changers in head and neck cancer: Future clinical and medicinal uses.
Hesham A. El-Mahdy,Ahmed M. Mohamadin,Ahmed I. Abulsoud,Emad Gamil Khidr,Ahmed A. El-Husseiny,Ahmed Ismail,Elsayed G.E. Elsakka,Hamada Ahmed Mokhlis,H. M. El-Husseiny,Ahmed S. Doghish +9 more
TL;DR: In this paper , a review of the relationship between miRNAs and head and neck cancers is presented, with a particular emphasis on how miRNA impact HNCs signaling networks, such as WNT/β-catenin signaling, PTEN/Akt/mTOR pathway, TGFβ, and KRAS mutations.
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Journal ArticleDOI
Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family
Leon N. Schulte,Leon N. Schulte,Ana Eulalio,Hans-Joachim Mollenkopf,Richard Reinhardt,Jörg Vogel,Jörg Vogel +6 more
TL;DR: In this article, cell type-dependent microRNA regulations upon infection of mammalian cells with the enteroinvasive pathogen, Salmonella Typhimurium, were reported.
Journal ArticleDOI
STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion.
Jung Mao Hsu,Weiya Xia,Yi Hsin Hsu,Li Chuan Chan,Li Chuan Chan,Wen Hsuan Yu,Wen Hsuan Yu,Jong Ho Cha,Jong Ho Cha,Chun-Te Chen,Hsin-Wei Liao,Hsin-Wei Liao,Hsin-Wei Liao,Chu Wei Kuo,Kay-Hooi Khoo,Jennifer L. Hsu,Jennifer L. Hsu,Chia Wei Li,Seung Oe Lim,Shih Shin Chang,Shih Shin Chang,Yi Chun Chen,Guo Xin Ren,Mien Chie Hung +23 more
TL;DR: The authors show that epithelial-mesenchymal transition induces glycosylation and stabilisation of PD-L1; antagonising this process renders cancer cells sensitive to anti-Tim3-therapy, revealing it as a potential strategy to enhance cancer immunotherapy efficacy.
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