TY - JOUR
T1 - Early tumor-infiltrating dendritic cells change their characteristics drastically in association with murine melanoma progression
AU - Nakahara, Takeshi
AU - Oba, Junna
AU - Shimomura, Chie
AU - Kido-Nakahara, Makiko
AU - Furue, Masutaka
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Number 25860951.
Publisher Copyright:
© 2015 The Authors. Published by Elsevier, Inc.
PY - 2016/1
Y1 - 2016/1
N2 - Dendritic cells (DCs) have a critical effect on the outcome of adaptive immune responses against growing tumors. Tumor-infiltrating dendritic cells (TIDCs) play diverse roles in the regulation of tumor regression or growth, but the characteristics that distinguish those effects are obscure. In this study, we investigated the frequency, phenotype, and function of TIDCs over time from early stages of melanoma growth in mice. Flow cytometric analysis revealed that the tumors were infiltrated by a significant population of CD11c+ major histocompatibility complex 11+ DCs, especially at an early stage of tumor growth. The allogeneic stimulatory capacity of TIDCs increased with tumor growth, whereas this capacity of DCs in lymph nodes decreased. TIDCs harvested at an early stage of melanoma (early TIDCs) accelerated tumor growth, but those harvested at a late stage (late TIDCs) delayed tumor progression when they were coinjected with melanoma cells. Furthermore, coinjection of early TIDCs failed to induce full immunocompetent maturation of CD8+ T cells, with much lower expression of IFN-γ, granzyme B, and perforin within the tumor microenvironment. In conclusion, TIDCs change their characteristics from an immunoinhibitory to an immunostimulatory phenotype over time in association with tumor progression.
AB - Dendritic cells (DCs) have a critical effect on the outcome of adaptive immune responses against growing tumors. Tumor-infiltrating dendritic cells (TIDCs) play diverse roles in the regulation of tumor regression or growth, but the characteristics that distinguish those effects are obscure. In this study, we investigated the frequency, phenotype, and function of TIDCs over time from early stages of melanoma growth in mice. Flow cytometric analysis revealed that the tumors were infiltrated by a significant population of CD11c+ major histocompatibility complex 11+ DCs, especially at an early stage of tumor growth. The allogeneic stimulatory capacity of TIDCs increased with tumor growth, whereas this capacity of DCs in lymph nodes decreased. TIDCs harvested at an early stage of melanoma (early TIDCs) accelerated tumor growth, but those harvested at a late stage (late TIDCs) delayed tumor progression when they were coinjected with melanoma cells. Furthermore, coinjection of early TIDCs failed to induce full immunocompetent maturation of CD8+ T cells, with much lower expression of IFN-γ, granzyme B, and perforin within the tumor microenvironment. In conclusion, TIDCs change their characteristics from an immunoinhibitory to an immunostimulatory phenotype over time in association with tumor progression.
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U2 - 10.1038/JID.2015.359
DO - 10.1038/JID.2015.359
M3 - Article
C2 - 26763434
AN - SCOPUS:84959484128
SN - 0022-202X
VL - 136
SP - 146
EP - 153
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 1
ER -