PD-L1-Mediated Immunosuppression in Oral Squamous Cell Carcinoma: Relationship With Macrophage Infiltration and Epithelial to Mesenchymal Transition Markers

• Published in: Frontiers in immunology Vol. 12; p. 693881
• Main Authors: Wu, Tiantian, Tang, Caijin, Tao, Renchuan, Yong, Xiangzhi, Jiang, Qiaozhi, Feng, Cong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 06-09-2021
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Cell Line, Tumor; chemical drugs; Chemokines - metabolism; Databases, Genetic; Epithelial-Mesenchymal Transition; Humans; Immune Checkpoint Inhibitors - therapeutic use; Immunology; immunosuppressive tumor microenvironment; macrophages; Mouth Neoplasms - drug therapy; Mouth Neoplasms - genetics; Mouth Neoplasms - immunology; Mouth Neoplasms - metabolism; PD-L1; Signal Transduction; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - immunology; Squamous Cell Carcinoma of Head and Neck - metabolism; Treatment Outcome; Tumor Microenvironment - immunology; Tumor-Associated Macrophages - immunology; Tumor-Associated Macrophages - metabolism; PD-L1; macrophages; epithelial-mesenchymal transition; chemical drugs; immunosuppressive tumor microenvironment
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.693881

To date, immune check-point inhibitors (ICIs), particularly inhibitors of programmed cell death-1 (PD-1) and PD ligand-1 (PD-L1) have become prominent in cancer treatment and also improved life expectancy of cancer patients. As key regulators of PD-1/PD-L1 axis, the recruitment of tumor-associated macrophages (TAMs) enhances aggressive and invasive properties of tumors in immunosuppressive tumor microenvironment (TME) and promotes epithelial-mesenchymal transition (EMT). The aims of the study were first to characterize the critical links among PD-L1, TME and EMT process and, further, to explore the sensitivity of different chemical agents to different PD-L1 expression groups. Bioinformatical analysis revealed that PD-L1 was highly expressed in OSCC and higher PD-L1 expression correlated with worse survival in patients. Notably, PD-L1 was positively correlated with macrophages infiltration and EMT markers gene expression. Moreover, patients in the PD-L1
group were at a significant chance of benefiting from ICI treatment and they also showed higher sensitivity to the chemical drugs (olaparib, paclitaxel, docetaxel, and pazopanib). These findings implicate PD-L1 could serve as a novel target for prognostic and therapeutic approaches in OSCC patients; PD-L1-mediated immune evasion might be attributable to the infiltration of macrophages, resulting EMT progress; Chemical agents in combination with PD-L1 inhibitor could be served as personalized treatment plan for OSCC patients so as to maximize patient benefit.