PMID- 30468994
OWN - NLM
STAT- MEDLINE
DCOM- 20190621
LR  - 20190621
IS  - 1879-1506 (Electronic)
IS  - 0003-9969 (Linking)
VI  - 98
DP  - 2019 Feb
TI  - Immune response and evasion mechanisms in lip carcinogenesis: An 
      immunohistochemical study.
PG  - 99-107
LID - S0003-9969(18)30645-9 [pii]
LID - 10.1016/j.archoralbio.2018.09.017 [doi]
AB  - OBJECTIVES: Programmed death ligand-1 (PD-L1) and human leukocyte antigen-G 
      (HLA-G) are considered immune checkpoint molecules that inhibit T-cell 
      effectiveness, contributing to tumor immune escape. This study investigated 
      PD-L1, HLA-G, CD8, and granzyme B (GrB) expression at different stages of lip 
      carcinogenesis. DESIGN AND RESULTS: Forty cases of lip squamous cell carcinoma 
      (LSCC), 55 actinic cheilitis (AC), and 10 healthy lip mucosa (HLM) were submitted 
      to immunohistochemistry. Semiquantitative (PD-L1, HLA-G), and quantitative (CD8, 
      GrB) analysis were performed. PD-L1 and HLA-G expression in neoplastic 
      cells/keratinocytes and stroma/connective tissue was significantly higher in LSCC 
      and AC, compared to HLM (p<0.05). PD-L1 was not associated with 
      clinicopathological features of the lesions. HLA-G expression by malignant cells 
      was significantly higher in LSCCs with distant metastasis (p = 0.041).CD8(+) and 
      GrB(+) cell numbers progressively increased from HLMs to LSCC, with AC exhibiting 
      intermediate numbers (p<0.01). Most LSCCs showed coexistence of PD-L1(+) and 
      CD8(+) cells (72.5%). PD-L1 was directly correlated to CD8(+) and GrB(+) 
      lymphocytic infiltration in LSCCs (p<0.05). Low cytotoxic immune response was 
      associated with lymph node metastasis in LSCC (p<0.05). CONCLUSIONS: PD-L1 and 
      HLA-G-mediated immune evasion mechanisms are likely to occur from early 
      pre-malignant to advanced malignant stages of lip carcinogenesis, which might 
      provide a rationale for therapeutic blockade of these pathways. PD-L1 expression 
      in LSCCs was correlated with the cytotoxic markers, suggesting that PD-L1 may 
      appear as an escape mechanism in response to an active antitumor response.
CI  - Copyright (c) 2018. Published by Elsevier Ltd.
FAU - Lopes, Maria Luiza Diniz de Sousa
AU  - Lopes MLDS
AD  - Post-Graduate Program in Oral Pathology, Department of Dentistry, Federal 
      University of Rio Grande do Norte, Natal, RN, Brazil.
FAU - Gonzaga, Amanda Katarinny Goes
AU  - Gonzaga AKG
AD  - Post-Graduate Program in Oral Pathology, Department of Dentistry, Federal 
      University of Rio Grande do Norte, Natal, RN, Brazil.
FAU - Mosconi, Carla
AU  - Mosconi C
AD  - Department of Stomatology (Oral Pathology), Dental School, Federal University of 
      Goias, Goiania, Brazil.
FAU - Palomino, Gustavo Martelli
AU  - Palomino GM
AD  - Division of Rheumatology, Faculty de Medicine, University of Sao Paulo 
      (FMRP-USP), Ribeirao Preto, Sao Paulo, Brazil.
FAU - Mendonca, Elismauro Francisco
AU  - Mendonca EF
AD  - Department of Stomatology (Oral Pathology), Dental School, Federal University of 
      Goias, Goiania, Brazil; Araujo Jorge Hospital, Association of Cancer Combat of 
      Goias, Division of Head and Neck and Department of Stomatology (Oral Pathology), 
      Dental School, Federal University of Goias, Goiania, Brazil.
FAU - Batista, Aline Carvalho
AU  - Batista AC
AD  - Department of Stomatology (Oral Pathology), Dental School, Federal University of 
      Goias, Goiania, Brazil.
FAU - Silveira, Ericka Janine Dantas da
AU  - Silveira EJDD
AD  - Post-Graduate Program in Oral Pathology, Department of Dentistry, Federal 
      University of Rio Grande do Norte, Natal, RN, Brazil. Electronic address: 
      ericka.janine@yahoo.com.br.
LA  - eng
PT  - Journal Article
DEP - 20180929
PL  - England
TA  - Arch Oral Biol
JT  - Archives of oral biology
JID - 0116711
RN  - 0 (HLA-G Antigens)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - EC 3.4.21.- (Granzymes)
RN  - Actinic cheilitis
SB  - IM
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Carcinogenesis/*immunology
MH  - Carcinoma, Squamous Cell/immunology/pathology
MH  - Cheilitis/immunology/pathology
MH  - Cross-Sectional Studies
MH  - Female
MH  - Granzymes/immunology
MH  - HLA-G Antigens/immunology
MH  - Humans
MH  - Immune Evasion
MH  - Immunohistochemistry
MH  - Keratinocytes/immunology/pathology
MH  - Lip Neoplasms/*immunology/pathology
MH  - Lymphatic Metastasis
MH  - Male
MH  - Middle Aged
MH  - Mouth Mucosa/immunology/pathology
MH  - Programmed Cell Death 1 Receptor/immunology
MH  - Retrospective Studies
MH  - Stromal Cells/immunology/pathology
MH  - Tumor Microenvironment/immunology
OTO - NOTNLM
OT  - Cheilitis, lip carcinogenesis
OT  - HLA-G
OT  - PD-L1
OT  - Squamous cell carcinoma
OT  - Tumor-infiltrating lymphocytes
EDAT- 2018/11/24 06:00
MHDA- 2019/06/22 06:00
CRDT- 2018/11/24 06:00
PHST- 2018/05/11 00:00 [received]
PHST- 2018/09/27 00:00 [revised]
PHST- 2018/09/28 00:00 [accepted]
PHST- 2018/11/24 06:00 [pubmed]
PHST- 2019/06/22 06:00 [medline]
PHST- 2018/11/24 06:00 [entrez]
AID - S0003-9969(18)30645-9 [pii]
AID - 10.1016/j.archoralbio.2018.09.017 [doi]
PST - ppublish
SO  - Arch Oral Biol. 2019 Feb;98:99-107. doi: 10.1016/j.archoralbio.2018.09.017. Epub 
      2018 Sep 29.