The Detection of Immunity against WT1 and SMAD4 P130L of EpCAM + Cancer Cells in Malignant Pleural Effusion.

Autor: Koya T; Department of Regenerative Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.; Center for Regenerative medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan., Niida Y; Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan., Togi M; Department of Regenerative Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.; Center for Regenerative medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan., Yoshida K; Center for Regenerative medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan., Sakamoto T; Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan., Ura H; Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan., Togi S; Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan., Kato T Jr; Division of Stem Cell Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan., Yamada S; Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan., Sugiyama H; Department of Cancer Immunology, Graduate School of Medicine, Osaka University, Suita 565-0871, Osaka, Japan., Koido S; Department of Gastroenterology and Hepatology, Jikei University School of Medicine, Kashiwa 277-8567, Chiba, Japan., Shimodaira S; Department of Regenerative Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.; Center for Regenerative medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan.; Division of Stem Cell Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Oct 12; Vol. 23 (20). Date of Electronic Publication: 2022 Oct 12.
DOI: 10.3390/ijms232012177
Abstrakt: Malignant pleural effusion (MPE) provides a liquid tumor microenvironment model that includes cancer cells and immune cells. However, the characteristics of tumor antigen-specific CD8 + T cells have not been investigated in detail. Here, we analyzed MPE samples taken from a patient with pancreatic cancer who received a dendritic cell vaccine targeting Wilms' Tumor 1 (WT1) antigen over the disease course (two points at MPE 1st and 2 nd , two months after MPE1 st ). Epithelial cell adhesion molecule (EpCAM) + cancer cells (PD-L1 - or T cell immunoglobulin mucin-3, TIM-3 - ), both PD-1 or TIM-3 positive CD8 + T cells, and CD14 + CD68 + CD163 + TIM-3 + macrophages increased from the MPE 1st to MPE 2nd . The ratio of WT1-specific cytotoxic lymphocytes (WT1-CTLs) to MPE CD8 + T cells and IFN-γ secretion of WT1-CTLs were reduced with disease progression. Coincidentally, the fraction of central memory T (T CM ) of WT1-CTLs was decreased. On the other hand, CD8 + T cells in response to SMAD4 P130L , which is homogeneously expressed in EpCAM + cancer cells, were detected using in vitro expansion with the HLA-A*11:01 restrictive SVCVNLYH neoantigen. Furthermore, the CD8 + T cell response to SMAD4 P130L was diminished following remarkably decreased numbers of CD8 + T CM in MPE samples. In conclusion, CD8 + T cells responding to WT1 or SMAD4 P130L neoantigen expressed in EpCAM + pancreatic cancer cells were detected in MPE. A tumor antigen-specific immune response would provide novel insight into the MPE microenvironment.
Databáze: MEDLINE
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