First Author | Ye J | Year | 2023 |
Journal | Eur J Immunol | Volume | 53 |
Issue | 9 | Pages | e2250160 |
PubMed ID | 37248998 | Mgi Jnum | J:343180 |
Mgi Id | MGI:7564374 | Doi | 10.1002/eji.202250160 |
Citation | Ye J, et al. (2023) Silencing of tumoral carbohydrate sulfotransferase 15 reactivates lymph node pancreatic cancer T cells in mice. Eur J Immunol 53(9):e2250160 |
abstractText | 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. |