YAP/STAT3 promotes the immune escape of larynx carcinoma by activating VEGFR1-TGFβ signaling to facilitate PD-L1 expression in M2-like TAMs

Journal Article · Sun Aug 15 04:00:00 EDT 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2021.112655· OSTI ID:23195557

Du, Xiao-Xiao ^[1]; He, Chao; Lu, Xiang ^[2]; Guo, Yu-Liang; Chen, Zhong-Hua ^[1]; Cai, Lan-Jun ^[2]

---

1. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Key Laboratory of Organ Transplantation, Ministry of Education & NHC Key Laboratory of Organ Transplantation & Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, 430030 (China)
2. Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 (China)

Larynx carcinoma (LC) is the most prevalent head and neck cancer among adults. LC xenograft mouse model was generated to verify the effect of VEGF on macrophage polarization and tumor growth in vivo. EdU assay was performed to measure the cell proliferation. Transwell assay was applied to assess cell migration. The expression of YAP and STAT3 was also significantly increased in LC tumor tissues. Moreover, both YAP and STAT3 overexpression in LC cells promoted the proliferation, migration, as well as the secretion of PD-L1 in M2-like TAMs. Mechanistically, the interaction between YAP and STAT3 facilitated the transcription of VEGF. Moreover, with a co-culture system, VEGF secretion in LC cells enhanced PD-L1 expression in M2-like TAMs via activating VEGFR1-TGFβ signaling pathway. Furthermore, VEGF secreted from LC cells also promoted the tumor growth of LC in vivo. We revealed that dysregulated YAP/STAT3 activity in LC cells could enhance the secretion of VEGF, which then functioned on M2-like TAMs via activating VEGFR1-TGFββ pathway to promote the expression of PD-L1 and immunosuppressive function of M2-like TAMs. Therefore, VEGF and PD-L1 might have a pivotal crosstalk between M2-like TAMs and LC cells, which provided a novel therapeutic target in regulating the metastasis of LC in future.

• OSTI ID: 23195557
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 405; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
CARCINOMAS
CELL PROLIFERATION
HEAD
IN VIVO
LARYNX
MACROPHAGES
METASTASES
MICE
NECK
SECRETION
TAMOXIFEN
TRANSCRIPTION