Silencing of tumoral carbohydrate sulfotransferase 15 reactivates lymph node pancreatic cancer T cells in mice.
Eur J Immunol
; 53(9): e2250160, 2023 09.
Article
en En
| MEDLINE
| ID: mdl-37248998
ABSTRACT
Limited intratumoral T-cell infiltration in pancreatic ductal adenocarcinoma (PDAC) is an obstacle to immunotherapy, yet the efficient approach to enhance tumor-infiltrating T cells is not fully established. Here, we show that tumor-specific knockdown of carbohydrate sulfotransferase 15 (CHST15), a tumor stromal proteoglycan-synthetic enzyme, suppresses tumor growth in a T-cell-dependent manner in a murine model of PDAC. Silencing of tumoral CHST15 unexpectedly expanded CD4+ and CD8+ T cells in tumor draining LN (TDLN), leading to accelerated accumulation of EdU+ proliferating CD4+ and CD8+ T cells and granzyme B+ CD8+ T cells in the tumor. RNA expression analysis indicated that tumoral CHST15 knockdown (KD) downregulated matrix remodeling-related genes, while upregulated anti-tumor T-cell activity-related genes in both tumor and TDLN. CHST15 KD significantly diminished intratumoral and TDLN Ly6C/G+ myeloid-derived suppressor cells prior to TDLN T-cell expansion, suggesting that tumoral CHST15 remotely regulated myeloid-derived suppressor cell mediated T-cell suppression in the TDLN. Our findings illustrate a novel immunotherapeutic potential of tumoral CHST15 blockage by reactivating T cells in immune suppressive TDLN of PDAC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Pancreáticas
/
Carcinoma Ductal Pancreático
/
Linfoma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón