PMID- 38058842
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231208
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 13
IP  - 11
DP  - 2023
TI  - Tenascin C in pancreatic cancer-associated fibroblasts enhances epithelial 
      mesenchymal transition and is associated with resistance to immune checkpoint 
      inhibitor.
PG  - 5641-5655
AB  - Tenascin C (TNC) is an extracellular matrix glycoprotein that is highly expressed 
      in cancer stroma and is associated with tumor progression in pancreatic 
      adenocarcinoma (PAAD). In this study, we aimed to investigate the potential 
      involvement of TNC in the response to immune checkpoint inhibitors (ICI) among 
      PAAD patients. Transcriptomic profiles were obtained from public databases and 
      analyzed to compare TNC mRNA levels between tumor and normal tissues. 
      Bioinformatic programs were used to predict paracrine communications between 
      cancer cells and cancer-associated fibroblasts (CAFs), and the Tumor Immune 
      Dysfunction and Exclusion (TIDE) score was calculated to predict response to ICI 
      treatment in PAAD patients. An independent immunotherapeutic cohort was used to 
      validate the clinical impact of the signatures. Results showed that TNC mRNA 
      levels were significantly upregulated in tumors compared to normal tissues in 
      PAAD, and patients with high TNC expression had significantly shorter overall 
      survival than those with low TNC expression (P = 0.0125). TNC was predominantly 
      expressed in CAFs of PAAD patients and was found to potentially enhance the 
      epithelial-mesenchymal transition (EMT) of cancer cells via integrin receptors, 
      contributing to resistance to ICI treatment. Patients with high TNC expression 
      and high ITGalphaV or ITGB3 expression were associated with poor response to ICI 
      therapy. In conclusion, these findings suggest that TNC-high CAFs play a crucial 
      role in tumor progression and resistance to ICI therapy in PAAD patients, and 
      targeting TNC and its interactions with cancer cells may provide a potential 
      strategy for improving the efficacy of ICI therapy in PAAD.
CI  - AJCR Copyright (c) 2023.
FAU - Furuhashi, Satoru
AU  - Furuhashi S
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
FAU - Morita, Yoshifumi
AU  - Morita Y
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
AD  - Division of Surgical Care, Hamamatsu University School of Medicine Morimachi, 
      Hamamatsu, Shizuoka, Japan.
FAU - Matsumoto, Akio
AU  - Matsumoto A
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
FAU - Ida, Shinya
AU  - Ida S
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
FAU - Muraki, Ryuta
AU  - Muraki R
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
FAU - Kitajima, Ryo
AU  - Kitajima R
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
FAU - Takeda, Makoto
AU  - Takeda M
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
FAU - Kikuchi, Hirotoshi
AU  - Kikuchi H
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
FAU - Hiramatsu, Yoshihiro
AU  - Hiramatsu Y
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
AD  - Department of Perioperative Functioning Care and Support, Hamamatsu University 
      School of Medicine Hamamatsu, Shizuoka, Japan.
FAU - Takeuchi, Hiroya
AU  - Takeuchi H
AD  - Department of Surgery, Hamamatsu University School of Medicine Hamamatsu, 
      Shizuoka, Japan.
LA  - eng
PT  - Journal Article
DEP - 20231115
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC10695794
OTO - NOTNLM
OT  - Tenascin C
OT  - cancer-associated fibroblast
OT  - epithelial-mesenchymal transition
OT  - immune checkpoint inhibitor
OT  - pancreatic adenocarcinoma
COIS- None.
EDAT- 2023/12/07 06:42
MHDA- 2023/12/07 06:43
PMCR- 2023/11/15
CRDT- 2023/12/07 04:11
PHST- 2023/05/08 00:00 [received]
PHST- 2023/11/06 00:00 [accepted]
PHST- 2023/12/07 06:43 [medline]
PHST- 2023/12/07 06:42 [pubmed]
PHST- 2023/12/07 04:11 [entrez]
PHST- 2023/11/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2023 Nov 15;13(11):5641-5655. eCollection 2023.