Accumulation of dysfunctional tumor-infiltrating PD-1+ DCs links PD-1/PD-L1 blockade immunotherapeutic response in cervical cancer

• Published in: Oncoimmunology Vol. 11; no. 1; p. 2034257
• Main Authors: Wang, Yu-meng, Qiu, Jun-jun, Qu, Xin-yu, Peng, Jing, Lu, Chong, Zhang, Meng, Zhang, Ming-Xing, Qi, Xing-ling, Lv, Bin, Guo, Jing-Jing, Guo, Chen-yan, Li, Gui-ling, Hua, Ke-qin
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 31.12.2022; Taylor & Francis Group
• Subjects: B7-H1 Antigen; cervical cancer; Dendritic cell; Dendritic Cells - metabolism; Female; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Interleukin-12 - metabolism; PD-1; predictive marker; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Tumor Necrosis Factor-alpha - metabolism; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - therapy; Dendritic cell; predictive marker; PD-1; cervical cancer; immunotherapy
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2022.2034257

Various predictive biomarkers are needed to select candidates for optimal and individualized treatments. Tumor-infiltrating immune cells have gained increasing interest in cancer research for the prediction of therapeutic response and survival. However, the role of dendritic cells (DCs) in PD-1 blockade immunotherapy remains unclear. In this study, we identified a population of PD-1+ DCs in the tumor microenvironment (TME) of cervical cancer (CC). The accumulation of PD-1+ DCs in cervical tumors was correlated with advanced stages, elevated preoperative squamous cell carcinoma antigen levels and lymph-vascular space invasion. PD-1 expression was induced on activated tumor-associated DCs (TADCs) in vitro compared with their resting counterparts. This PD-1+ DC population was characterized by reduced secretion of cytokines (IL-12, TNF-α, and IL-1β) and dysfunctional induction of T cell proliferation and cytotoxic reaction. PD-1 blockade significantly reinvigorated PD-1+ DCs to release IL-12, TNF-α, and IL-1β compared with PD-1- DCs. TILs from samples with higher PD-1+ DC infiltration could be induced to achieve a greater killing effect of PD-1 blockade treatment. Our findings suggested a role for PD-1+ DCs in immune surveillance dysfunction and CC progression. PD-1+ DC density in the TME may serve as a diagnostic factor for predicting the optimal beneficiaries of PD-1/PD-L1 blockade immunotherapy in CC.