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The Detection of Immunity against WT1 and SMAD4 P130L of EpCAM + Cancer Cells in Malignant Pleural Effusion.
- Source :
- International Journal of Molecular Sciences; Oct2022, Vol. 23 Issue 20, p12177-N.PAG, 11p
- Publication Year :
- 2022
-
Abstract
- 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<superscript>+</superscript> 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<superscript>1st</superscript> and 2<superscript>nd</superscript>, two months after MPE1<superscript>st</superscript>). Epithelial cell adhesion molecule (EpCAM)<superscript>+</superscript> cancer cells (PD-L1<superscript>−</superscript> or T cell immunoglobulin mucin-3, TIM-3<superscript>−</superscript>), both PD-1 or TIM-3 positive CD8<superscript>+</superscript> T cells, and CD14<superscript>+</superscript>CD68<superscript>+</superscript>CD163<superscript>+</superscript>TIM-3<superscript>+</superscript> macrophages increased from the MPE<superscript>1st</superscript> to MPE<superscript>2nd</superscript>. The ratio of WT1-specific cytotoxic lymphocytes (WT1-CTLs) to MPE CD8<superscript>+</superscript> T cells and IFN-γ secretion of WT1-CTLs were reduced with disease progression. Coincidentally, the fraction of central memory T (T<subscript>CM</subscript>) of WT1-CTLs was decreased. On the other hand, CD8<superscript>+</superscript> T cells in response to SMAD4<superscript>P130L</superscript>, which is homogeneously expressed in EpCAM<superscript>+</superscript> cancer cells, were detected using in vitro expansion with the HLA-A*11:01 restrictive SVCVNLYH neoantigen. Furthermore, the CD8<superscript>+</superscript> T cell response to SMAD4<superscript>P130L</superscript> was diminished following remarkably decreased numbers of CD8<superscript>+</superscript> T<subscript>CM</subscript> in MPE samples. In conclusion, CD8<superscript>+</superscript> T cells responding to WT1 or SMAD4<superscript>P130L</superscript> neoantigen expressed in EpCAM<superscript>+</superscript> pancreatic cancer cells were detected in MPE. A tumor antigen-specific immune response would provide novel insight into the MPE microenvironment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 23
- Issue :
- 20
- Database :
- Complementary Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 159904859
- Full Text :
- https://doi.org/10.3390/ijms232012177