PMID- 37248998
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20240102
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 53
IP  - 9
DP  - 2023 Sep
TI  - Silencing of tumoral carbohydrate sulfotransferase 15 reactivates lymph node 
      pancreatic cancer T cells in mice.
PG  - e2250160
LID - 10.1002/eji.202250160 [doi]
AB  - 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.
CI  - (c) 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
FAU - Ye, Juanjuan
AU  - Ye J
AD  - Oncology Pathology, Department of Pathology and Host-Defense, Faculty of 
      Medicine, Kagawa University, Kagawa, Japan.
FAU - Suizu, Futoshi
AU  - Suizu F
AD  - Oncology Pathology, Department of Pathology and Host-Defense, Faculty of 
      Medicine, Kagawa University, Kagawa, Japan.
FAU - Yamakawa, Keiko
AU  - Yamakawa K
AD  - Oncology Pathology, Department of Pathology and Host-Defense, Faculty of 
      Medicine, Kagawa University, Kagawa, Japan.
FAU - Mukai, Yuri
AU  - Mukai Y
AD  - Oncology Pathology, Department of Pathology and Host-Defense, Faculty of 
      Medicine, Kagawa University, Kagawa, Japan.
FAU - Kato, Motohiko
AU  - Kato M
AD  - Division of Research and Development for Minimally Invasive Treatment, Cancer 
      Center, Keio University School of Medicine, Tokyo, Japan.
FAU - Yoneyama, Hiroyuki
AU  - Yoneyama H
AD  - TME Therapeutics Inc. Minato-ku, Tokyo, Japan.
FAU - Yahagi, Naohisa
AU  - Yahagi N
AD  - Division of Research and Development for Minimally Invasive Treatment, Cancer 
      Center, Keio University School of Medicine, Tokyo, Japan.
FAU - Matsuda, Yoko
AU  - Matsuda Y
AD  - Oncology Pathology, Department of Pathology and Host-Defense, Faculty of 
      Medicine, Kagawa University, Kagawa, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230530
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
SB  - IM
MH  - Animals
MH  - Mice
MH  - CD8-Positive T-Lymphocytes
MH  - *Pancreatic Neoplasms/genetics
MH  - *Carcinoma, Pancreatic Ductal/genetics/metabolism
MH  - *Lymphoma
MH  - Lymph Nodes
MH  - Mice, Inbred C57BL
MH  - Carbohydrate Sulfotransferases
OTO - NOTNLM
OT  - Myeloid-derived suppressor cells (MDSCs)
OT  - Pancreatic ductal adenocarcinoma (PDAC)
OT  - T cell
OT  - Tumor draining lymph node (TDLN)
EDAT- 2023/05/30 06:42
MHDA- 2023/09/11 06:42
CRDT- 2023/05/30 05:28
PHST- 2023/05/16 00:00 [revised]
PHST- 2022/09/24 00:00 [received]
PHST- 2023/05/17 00:00 [accepted]
PHST- 2023/09/11 06:42 [medline]
PHST- 2023/05/30 06:42 [pubmed]
PHST- 2023/05/30 05:28 [entrez]
AID - 10.1002/eji.202250160 [doi]
PST - ppublish
SO  - Eur J Immunol. 2023 Sep;53(9):e2250160. doi: 10.1002/eji.202250160. Epub 2023 May 
      30.