PMID- 26763434 OWN - NLM STAT- MEDLINE DCOM- 20160520 LR - 20210103 IS - 1523-1747 (Electronic) IS - 0022-202X (Linking) VI - 136 IP - 1 DP - 2016 Jan TI - Early Tumor-Infiltrating Dendritic Cells Change their Characteristics Drastically in Association with Murine Melanoma Progression. PG - 146-53 LID - S0022-202X(15)00009-3 [pii] LID - 10.1038/JID.2015.359 [doi] 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 II(+) 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-gamma, 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. CI - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Nakahara, Takeshi AU - Nakahara T AD - Division of Skin Surface Sensing, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: nakahara@dermatol.med.kyushu-u.ac.jp. FAU - Oba, Junna AU - Oba J AD - Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Shimomura, Chie AU - Shimomura C AD - Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Kido-Nakahara, Makiko AU - Kido-Nakahara M AD - Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Furue, Masutaka AU - Furue M AD - Division of Skin Surface Sensing, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 SB - IM MH - Animals MH - Cell Transformation, Neoplastic/*pathology MH - Dendritic Cells/cytology/*pathology MH - Disease Models, Animal MH - Disease Progression MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Flow Cytometry MH - Melanoma/*pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Random Allocation MH - Real-Time Polymerase Chain Reaction/methods MH - Sensitivity and Specificity MH - Skin Neoplasms/*pathology/physiopathology MH - *Tumor Burden EDAT- 2016/01/15 06:00 MHDA- 2016/05/21 06:00 CRDT- 2016/01/15 06:00 PHST- 2015/03/12 00:00 [received] PHST- 2015/08/13 00:00 [revised] PHST- 2015/08/27 00:00 [accepted] PHST- 2016/01/15 06:00 [entrez] PHST- 2016/01/15 06:00 [pubmed] PHST- 2016/05/21 06:00 [medline] AID - S0022-202X(15)00009-3 [pii] AID - 10.1038/JID.2015.359 [doi] PST - ppublish SO - J Invest Dermatol. 2016 Jan;136(1):146-53. doi: 10.1038/JID.2015.359.