TY - JOUR
T1 - Crucial role of dendritic cells in the generation of anti-tumor T-cell responses and immunogenic tumor microenvironment to suppress tumor development
AU - Tominaga, Moe
AU - Uto, Tomofumi
AU - Fukaya, Tomohiro
AU - Mitoma, Shuya
AU - Riethmacher, Dieter
AU - Umekita, Kunihiko
AU - Yamashita, Yoshihiro
AU - Sato, Katsuaki
N1 - Publisher Copyright:
Copyright © 2024 Tominaga, Uto, Fukaya, Mitoma, Riethmacher, Umekita, Yamashita and Sato.
PY - 2024
Y1 - 2024
N2 - Dendritic cells (DCs) are known as unique professional antigen (Ag)-presenting cells (APCs) to prime naïve T cells for the initiation of adaptive immunity. While DCs are believed to play a pivotal role in generating anti-tumor T-cell responses, the importance of DCs in the protection from the progression of tumors remains elusive. Here, we show how the constitutive deficiency of CD11chi DCs influences the progression of tumors with the use of binary transgenic mice with constitutive loss of CD11chi DCs. Constitutive loss of CD11chi DCs not only enhances the progression of tumors but also reduces the responses of Ag-specific T cells. Furthermore, the congenital deficiency of CD11chi DCs generates the immunosuppressive tumor microenvironment (TME) that correlates with the marked accumulation of myeloid-derived suppressor cells (MDSCs) and the prominent productions of immunosuppressive mediators. Thus, our findings suggest that CD11chi DCs are crucial for generating anti-tumor T-cell responses and immunogenic TME to suppress the development of tumors.
AB - Dendritic cells (DCs) are known as unique professional antigen (Ag)-presenting cells (APCs) to prime naïve T cells for the initiation of adaptive immunity. While DCs are believed to play a pivotal role in generating anti-tumor T-cell responses, the importance of DCs in the protection from the progression of tumors remains elusive. Here, we show how the constitutive deficiency of CD11chi DCs influences the progression of tumors with the use of binary transgenic mice with constitutive loss of CD11chi DCs. Constitutive loss of CD11chi DCs not only enhances the progression of tumors but also reduces the responses of Ag-specific T cells. Furthermore, the congenital deficiency of CD11chi DCs generates the immunosuppressive tumor microenvironment (TME) that correlates with the marked accumulation of myeloid-derived suppressor cells (MDSCs) and the prominent productions of immunosuppressive mediators. Thus, our findings suggest that CD11chi DCs are crucial for generating anti-tumor T-cell responses and immunogenic TME to suppress the development of tumors.
KW - anti-tumor T-cell responses
KW - dendritic cells
KW - immunosuppressive mediators
KW - myeloid-derived suppressor cells
KW - tumor development
KW - tumor microenvironment
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U2 - 10.3389/fimmu.2024.1200461
DO - 10.3389/fimmu.2024.1200461
M3 - Article
AN - SCOPUS:85202181147
SN - 1664-3224
VL - 15
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1200461
ER -