PMID- 34310369
OWN - NLM
STAT- MEDLINE
DCOM- 20210924
LR  - 20230922
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 45
IP  - 9
DP  - 2021 Sep 1
TI  - Human Leukocyte Antigen Class I Deficiency in Gastric Carcinoma: An Adaptive 
      Immune Evasion Strategy Most Common in Microsatellite Instable Tumors.
PG  - 1213-1220
LID - 10.1097/PAS.0000000000001779 [doi]
AB  - Immune checkpoint inhibitor therapy is effective only for a subset of patients 
      with gastric cancer. Impaired neoantigen presentation caused by deficiency of 
      human leukocyte antigen class I (HLA-I) has been reported as a common mechanism 
      of immune evasion which is associated with resistance to immune checkpoint 
      blockade. To elucidate the significance of HLA-I deficiency in gastric cancer 
      with special focus on microsatellite instable (MSI) and Epstein-Barr virus 
      (EBV)-positive tumors, we examined HLA-I expression on tumor cells and correlated 
      the results with clinicopathologic features, programmed death-ligand 1 (PD-L1) 
      expression, and degree of tumor-infiltrating immune cells. This study included 58 
      MSI, 44 EBV-positive, and 107 non-EBV non-MSI tumors for comparison. The 
      frequency of HLA-I deficiency (>/=1% tumor cells) was significantly higher in MSI 
      tumors (52%) compared with EBV-positive tumors (23%) and the other tumors (28%). 
      In contrast, PD-L1 expression levels were highest in EBV-positive tumors, 
      followed by MSI tumors, with the lowest prevalence in the other tumors in both 
      Tumor Proportion Score and Combined Positive Score. HLA-I deficiency was 
      significantly more frequent in advanced tumors (pT2-4) than in early tumors (pT1) 
      in MSI and non-EBV non-MSI subtypes. In addition, the degree of CD8-positive 
      cells infiltration was significantly reduced in HLA-I deficient tumor areas 
      compared with HLA-I preserved tumor area within a tumor. Based on our 
      observations, HLA-I, as well as PD-L1, should be considered as a common mechanism 
      of immune escape especially in the MSI subtype, and therefore could be a 
      biomarker predicting response to immune checkpoint inhibitor therapy in gastric 
      cancer.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Iwasaki, Akiko
AU  - Iwasaki A
AD  - Departments of Pathology.
FAU - Shinozaki-Ushiku, Aya
AU  - Shinozaki-Ushiku A
AD  - Departments of Pathology.
FAU - Kunita, Akiko
AU  - Kunita A
AD  - Departments of Pathology.
FAU - Yamazawa, Sho
AU  - Yamazawa S
AD  - Departments of Pathology.
FAU - Sato, Yasuyoshi
AU  - Sato Y
AD  - Gastrointestinal Surgery, The University of Tokyo.
FAU - Yamashita, Hiroharu
AU  - Yamashita H
AD  - Department of Digestive Surgery, Nihon University School of Medicine, Tokyo.
FAU - Fukayama, Masashi
AU  - Fukayama M
AD  - Asahi TelePathology Center, Asahi General Hospital, Asahi, Chiba Prefecture, 
      Japan.
FAU - Seto, Yasuyuki
AU  - Seto Y
AD  - Gastrointestinal Surgery, The University of Tokyo.
FAU - Ushiku, Tetsuo
AU  - Ushiku T
AD  - Departments of Pathology.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CD274 protein, human)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - B7-H1 Antigen/metabolism
MH  - Biomarkers, Tumor/*immunology
MH  - Epstein-Barr Virus Infections/complications
MH  - Female
MH  - Histocompatibility Antigens Class I/immunology/*metabolism
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating/immunology
MH  - Male
MH  - Microsatellite Instability
MH  - Middle Aged
MH  - Stomach Neoplasms/*immunology
MH  - Tumor Escape/*immunology
COIS- Conflicts of Interest and Source of Funding: Supported by a Grant-in Aid for 
      Scientific Research from the Japan Society for the Promotion of Science (18K06983 
      for T.U.). The authors have disclosed that they have no significant relationships 
      with, or financial interest in, any commercial companies pertaining to this 
      article.
EDAT- 2021/07/27 06:00
MHDA- 2021/09/25 06:00
CRDT- 2021/07/26 17:21
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/09/25 06:00 [medline]
PHST- 2021/07/26 17:21 [entrez]
AID - 00000478-202109000-00006 [pii]
AID - 10.1097/PAS.0000000000001779 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2021 Sep 1;45(9):1213-1220. doi: 10.1097/PAS.0000000000001779.