PMID- 37686454
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20230911
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 17
DP  - 2023 Sep 4
TI  - HLA Class I Expression Is Associated with DNA Damage and Immune Cell Infiltration 
      into Dysplastic and Neoplastic Lesions in Ulcerative Colitis.
LID - 10.3390/ijms241713648 [doi]
LID - 13648
AB  - Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for 
      ulcerative colitis (UC). This study aimed to investigate the significance of DNA 
      damage and HLA-I expression in infiltrating immune cells and immune checkpoint 
      protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal 
      cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, gammaH2AX 
      (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 
      (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal 
      mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane 
      HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly 
      higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was 
      associated with high positivity of gammaH2AX and PD-L1 expression compared to SCRC. 
      The infiltration of CD8-positive T cells and CD68-positive macrophages in 
      HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. 
      Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive 
      epithelial cells with high CD8- and CD68-positive immune cell infiltration 
      compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune 
      cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating 
      DNA damage-induced HLA-I antigen presentation.
FAU - Okami, Haruka
AU  - Okami H
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Ozawa, Naoya
AU  - Ozawa N
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Sohda, Makoto
AU  - Sohda M
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Yokobori, Takehiko
AU  - Yokobori T
AUID- ORCID: 0000-0003-3284-4796
AD  - Division of Integrated Oncology Research, Gunma University, Initiative for 
      Advanced Research (GIAR), Maebashi 371-8511, Japan.
FAU - Osone, Katsuya
AU  - Osone K
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Erkhem-Ochir, Bilguun
AU  - Erkhem-Ochir B
AD  - Division of Integrated Oncology Research, Gunma University, Initiative for 
      Advanced Research (GIAR), Maebashi 371-8511, Japan.
FAU - Dorjkhorloo, Gendensuren
AU  - Dorjkhorloo G
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Shiraishi, Takuya
AU  - Shiraishi T
AUID- ORCID: 0000-0003-3543-1874
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Okada, Takuhisa
AU  - Okada T
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Sano, Akihiko
AU  - Sano A
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Sakai, Makoto
AU  - Sakai M
AUID- ORCID: 0000-0003-0860-3132
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Miyazaki, Tatsuya
AU  - Miyazaki T
AD  - Department of Surgery Japanese Red Cross Maebashi Hospital, Maebashi 371-0811, 
      Japan.
FAU - Ogawa, Hiroomi
AU  - Ogawa H
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Yao, Takashi
AU  - Yao T
AUID- ORCID: 0000-0003-2287-7658
AD  - Department of Human Pathology, Graduate School of Medicine, Juntendo University, 
      Bunkyo-ku 113-8431, Japan.
FAU - Oike, Takahiro
AU  - Oike T
AD  - Department of Radiation Oncology, Graduate School of Medicine, Gunma University, 
      Maebashi 371-8510, Japan.
FAU - Sato, Hiro
AU  - Sato H
AUID- ORCID: 0000-0001-8267-6917
AD  - Department of Radiation Oncology, Graduate School of Medicine, Gunma University, 
      Maebashi 371-8510, Japan.
FAU - Shirabe, Ken
AU  - Shirabe K
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
FAU - Shibata, Atsushi
AU  - Shibata A
AD  - Division of Molecular Oncological Pharmacy, Faculty of Pharmacy, Keio University, 
      Minato-ku 108-8345, Japan.
FAU - Saeki, Hiroshi
AU  - Saeki H
AD  - Department of General Surgical Science, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8510, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230904
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Immune Checkpoint Proteins)
SB  - IM
MH  - Humans
MH  - *B7-H1 Antigen/genetics
MH  - *Colitis, Ulcerative/genetics
MH  - Hyperplasia
MH  - Epithelial Cells
MH  - DNA Damage
MH  - Immune Checkpoint Proteins
PMC - PMC10487850
OTO - NOTNLM
OT  - DNA damage
OT  - colitic cancer
OT  - human leukocyte antigen
OT  - immune cells
COIS- The authors have no conflict of interest.
EDAT- 2023/09/09 11:47
MHDA- 2023/09/11 06:43
PMCR- 2023/09/04
CRDT- 2023/09/09 01:14
PHST- 2023/07/26 00:00 [received]
PHST- 2023/08/24 00:00 [revised]
PHST- 2023/09/02 00:00 [accepted]
PHST- 2023/09/11 06:43 [medline]
PHST- 2023/09/09 11:47 [pubmed]
PHST- 2023/09/09 01:14 [entrez]
PHST- 2023/09/04 00:00 [pmc-release]
AID - ijms241713648 [pii]
AID - ijms-24-13648 [pii]
AID - 10.3390/ijms241713648 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Sep 4;24(17):13648. doi: 10.3390/ijms241713648.