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Protein tyrosine kinases in dendritic cell-mediated anti-cancer immunity
Misha Mao1, Liwei Zhao2, Guido Kroemer3
1General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China; Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China; Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Inserm, Université Paris Cité, Sorbonne Université, Paris, France; Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Institut, Villejuif, France.
Abstract:
Dendritic cells (DCs), the most proficient antigen-presenting cells, bridge innate and adaptive immunity and are critical for anti-cancer immune surveillance. Their function is precisely regulated by protein tyrosine kinases (PTKs), which integrate signals from external stimuli and internal cellular stress to control DC maturation, migration, and antigen presentation. This review systematically synthesizes current knowledge on PTK roles in DC-mediated anti-tumor immunity, with a focused analysis of their differential expression and function across human and mouse DC subsets-including conventional (cDC1, cDC2), plasmacytoid (pDC), and monocyte-derived DCs. We highlight how specific PTK families (e.g., TAM, PDGFR, SRC, JAK) translate pathogen- and damage-associated signals into tailored immune responses. Furthermore, we discuss the dual impact of clinically approved PTK inhibitors on DC function, which can either enhance or suppress anti-tumor immunity depending on context. Finally, we evaluate translational strategies that combine PTK-targeted agents with DC-based vaccines or immune checkpoint blockade, offering a rationale for exploiting PTK-DC crosstalk to develop more effective combinatorial immunotherapies.
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