| RRC ID |
78697
|
| Author |
Ye J, Suizu F, Yamakawa K, Mukai Y, Kato M, Yoneyama H, Yahagi N, Matsuda Y.
|
| Title |
Silencing of tumoral carbohydrate sulfotransferase 15 reactivates lymph node pancreatic cancer T cells in mice.
|
| Journal |
Eur J Immunol
|
| 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.
|
| Volume |
53(9)
|
| Pages |
e2250160
|
| Published |
2023-9-1
|
| DOI |
10.1002/eji.202250160
|
| PMID |
37248998
|
| MeSH |
Animals
CD8-Positive T-Lymphocytes
Carbohydrate Sulfotransferases
Carcinoma, Pancreatic Ductal* / genetics
Carcinoma, Pancreatic Ductal* / metabolism
Lymph Nodes
Lymphoma*
Mice
Mice, Inbred C57BL
Pancreatic Neoplasms* / genetics
|
| Resource |
| Human and Animal Cells |
CTLL-2(RCB0637) |
