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Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.

Abstract Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title plos one
Publication Year Start




PMID- 28423034
OWN - NLM
STAT- In-Process
DA  - 20170419
LR  - 20170419
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 4
DP  - 2017
TI  - Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within
      tumour from perineural squamous cell carcinoma patients.
PG  - e0175755
LID - 10.1371/journal.pone.0175755 [doi]
AB  - Perineural spread of tumour cells along cranial nerves is a severe complication
      of primary cutaneous squamous cell carcinomas of the head and neck region. While 
      surgical excision of the tumour is the treatment of choice, removal of all the
      tumour is often complicated by the neural location and recurrence is frequent.
      Non-invasive immune treatments such as checkpoint inhibitor blockade may be
      useful in this set of tumours although little is understood about the immune
      response to perineural spread of squamous cell carcinomas. Immunohistochemistry
      studies suggest that perineural tumour contains a lymphocyte infiltrate but it is
      difficult to quantitate the different proportions of immune cell subsets and
      expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow
      cytometry of excised perineural tumour tissue, we show that a T cell infiltrate
      is prominent in addition to less frequent B cell, NK cell and NKT cell
      infiltrates. CD8 T cells are more frequent than other T cells in the tumour
      tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing
      cells was significantly greater in the tumour relative to the blood, a pattern
      that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using
      immunohistochemistry, PD-1 and PD-L1-expression could be detected in close
      proximity amongst perineural tumour tissue. The data suggest that perineural SCC 
      contains a mixture of immune cells with a predominant T cell infiltrate
      containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+
      and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local
      antibody blockade of these checkpoint inhibitors.
FAU - Linedale, Richard
AU  - Linedale R
AD  - The University of Queensland Diamantina Institute, The University of Queensland, 
      Translational Research Institute, Brisbane, Australia.
FAU - Schmidt, Campbell
AU  - Schmidt C
AD  - The University of Queensland Diamantina Institute, The University of Queensland, 
      Translational Research Institute, Brisbane, Australia.
AD  - Department of Otolaryngology-Head and Neck Surgery, Princess Alexandra Hospital, 
      Brisbane, Australia.
AD  - The University of Queensland Faculty of Medicine, Brisbane, Australia.
FAU - King, Brigid T
AU  - King BT
AD  - The University of Queensland Diamantina Institute, The University of Queensland, 
      Translational Research Institute, Brisbane, Australia.
AD  - The University of Queensland Faculty of Medicine, Brisbane, Australia.
FAU - Ganko, Annabelle G
AU  - Ganko AG
AD  - The University of Queensland Diamantina Institute, The University of Queensland, 
      Translational Research Institute, Brisbane, Australia.
AD  - The University of Queensland Faculty of Medicine, Brisbane, Australia.
FAU - Simpson, Fiona
AU  - Simpson F
AD  - The University of Queensland Diamantina Institute, The University of Queensland, 
      Translational Research Institute, Brisbane, Australia.
FAU - Panizza, Benedict J
AU  - Panizza BJ
AD  - Department of Otolaryngology-Head and Neck Surgery, Princess Alexandra Hospital, 
      Brisbane, Australia.
AD  - The University of Queensland Faculty of Medicine, Brisbane, Australia.
FAU - Leggatt, Graham R
AU  - Leggatt GR
AUID- ORCID: http://orcid.org/0000-0002-4078-5653
AD  - The University of Queensland Diamantina Institute, The University of Queensland, 
      Translational Research Institute, Brisbane, Australia.
LA  - eng
PT  - Journal Article
DEP - 20170419
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
EDAT- 2017/04/20 06:00
MHDA- 2017/04/20 06:00
CRDT- 2017/04/20 06:00
PHST- 2016/11/15 [received]
PHST- 2017/03/30 [accepted]
AID - 10.1371/journal.pone.0175755 [doi]
AID - PONE-D-16-45327 [pii]
PST - epublish
SO  - PLoS One. 2017 Apr 19;12(4):e0175755. doi: 10.1371/journal.pone.0175755.
      eCollection 2017.

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