PMID- 32383556
OWN - NLM
STAT- MEDLINE
DCOM- 20210503
LR  - 20210503
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 9
IP  - 13
DP  - 2020 Jul
TI  - Characterization of the immune profile of oral tongue squamous cell carcinomas 
      with advancing disease.
PG  - 4791-4807
LID - 10.1002/cam4.3106 [doi]
AB  - We investigated whether a unique immune response was instigated with the 
      development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal 
      involvement, with/without recurrent metastatic disease, or within tumor involved 
      nodes. One hundred and ten formalin-fixed paraffin-embedded samples were 
      collected from a retrospective cohort of 67 OTSCC patients and 10 non-cancerous 
      tongue samples. Targets including CD4, CD8, FOXP3, PD-L1, and PD-1 were analyzed 
      by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used 
      for gene expression profiling. Data were externally validated in the The Cancer 
      Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell 
      carcinoma (LSCC) cohorts. A 24-immune gene signature was identified that 
      discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC 
      was associated with survival in other TCGA cohorts (improved survival for 
      melanoma, P < .001 and worse survival for LSCC, P = .038). OTSCC exhibited 
      concordant gene and immunohistochemical (IHC) features characterized by a TH-2 
      biased, proinflammatory profile with upregulated B cell and neutrophil gene 
      activity and increased CD4, FOXP3, and PD-L1 expression (P < .001 for all by 
      IHC). Compared to less advanced disease, nodal involvement and recurrent OTSCC 
      did not induce a different immune response although recurrent disease was 
      characterized by significantly higher PD-L1 expression (P = .004 by SP263, 
      P = .013 by 22C3, P = .004 for gene expression). Identification of a gene 
      signature associated with different prognostic effects in other cancers 
      highlights common pathways of immune dysregulation that are impacted by the tumor 
      origin. The significant immunosuppressive signaling in OTSCC indicates primary 
      failure of immune system to control carcinogenesis emphasizing the need for 
      early, combination therapeutic approaches.
CI  - (c) 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Meehan, Katie
AU  - Meehan K
AD  - Chinese University of Hong Kong, Hong Kong.
FAU - Leslie, Connull
AU  - Leslie C
AD  - Department of Anatomical Pathology, PathWest Laboratory Medicine, Queen Elizabeth 
      Medical Centre, Nedlands, WA, Australia.
FAU - Lucas, Michaela
AU  - Lucas M
AD  - University of Western Australia, Crawley, WA, Australia.
AD  - Department of Clinical Immunology, PathWest and Sir Charles Gairdner Hospital, 
      Queen Elizabeth Medical Centre, Nedlands, WA, Australia.
FAU - Jacques, Angela
AU  - Jacques A
AD  - Institute for Health Research, University of Notre Dame, Fremantle, WA, 
      Australia.
AD  - Department of Research, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
FAU - Mirzai, Bob
AU  - Mirzai B
AD  - Department of Anatomical Pathology, PathWest Laboratory Medicine, Queen Elizabeth 
      Medical Centre, Nedlands, WA, Australia.
AD  - University of Western Australia, Crawley, WA, Australia.
FAU - Lim, James
AU  - Lim J
AD  - Genomics WA, Telethon Kids Institute, West Perth, WA, Australia.
FAU - Bulsara, Max
AU  - Bulsara M
AD  - Institute for Health Research, University of Notre Dame, Fremantle, WA, 
      Australia.
FAU - Khan, Yasir
AU  - Khan Y
AD  - Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, 
      Australia.
FAU - Wong, Nicholas C
AU  - Wong NC
AD  - Monash Bioinformatics Platform, Monash University, Clayton, VIC, Australia.
FAU - Solomon, Benjamin
AU  - Solomon B
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
AD  - Department of Oncology, Sir Peter MacCallum, The University of Melbourne, 
      Melbourne, VIC, Australia.
FAU - Sader, Chady
AU  - Sader C
AD  - University of Western Australia, Crawley, WA, Australia.
AD  - Department of Otolaryngology, Head and Neck, Skull Base Surgery, Sir Charles 
      Gairdner Hospital, Nedlands, WA, Australia.
FAU - Friedland, Peter
AU  - Friedland P
AD  - University of Western Australia, Crawley, WA, Australia.
AD  - Department of Otolaryngology, Head and Neck, Skull Base Surgery, Sir Charles 
      Gairdner Hospital, Nedlands, WA, Australia.
AD  - School of Medicine, University of Notre Dame, Fremantle, WA, Australia.
FAU - Mir Arnau, Gisela
AU  - Mir Arnau G
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Semple, Timothy
AU  - Semple T
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Lim, Annette M
AU  - Lim AM
AUID- ORCID: 0000-0002-0777-2279
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
AD  - Department of Oncology, Sir Peter MacCallum, The University of Melbourne, 
      Melbourne, VIC, Australia.
LA  - eng
PT  - Journal Article
DEP - 20200508
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (CD4 Antigens)
RN  - 0 (CD8 Antigens)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
MH  - Aged
MH  - B7-H1 Antigen/analysis
MH  - CD4 Antigens/analysis
MH  - CD8 Antigens/analysis
MH  - Female
MH  - Forkhead Transcription Factors/analysis
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Humans
MH  - Lung Neoplasms/immunology/mortality
MH  - Lymph Nodes/pathology
MH  - Male
MH  - Melanoma/immunology/mortality
MH  - Middle Aged
MH  - Prognosis
MH  - Programmed Cell Death 1 Receptor/analysis
MH  - Retrospective Studies
MH  - Squamous Cell Carcinoma of Head and Neck/genetics/*immunology/mortality/pathology
MH  - Tongue/immunology
MH  - Tongue Neoplasms/genetics/*immunology/mortality/pathology
PMC - PMC7333861
OTO - NOTNLM
OT  - FOXP3
OT  - Immune signature
OT  - PD-L1
OT  - oral tongue squamous cell carcinoma
COIS- AM Lim - uncompensated advisory board from Merck Sharp & Dohme and Bristol-Myers 
      Squibb with travel and accommodation expenses. The other authors declare that 
      there is no potential conflict of interest.
EDAT- 2020/05/10 06:00
MHDA- 2021/05/04 06:00
PMCR- 2020/05/08
CRDT- 2020/05/09 06:00
PHST- 2019/12/11 00:00 [received]
PHST- 2020/03/13 00:00 [revised]
PHST- 2020/04/17 00:00 [accepted]
PHST- 2020/05/10 06:00 [pubmed]
PHST- 2021/05/04 06:00 [medline]
PHST- 2020/05/09 06:00 [entrez]
PHST- 2020/05/08 00:00 [pmc-release]
AID - CAM43106 [pii]
AID - 10.1002/cam4.3106 [doi]
PST - ppublish
SO  - Cancer Med. 2020 Jul;9(13):4791-4807. doi: 10.1002/cam4.3106. Epub 2020 May 8.