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

Linedale, Richard, Schmidt, Campbell, King, Brigid T., Ganko, Annabelle G., Simpson, Fiona, Panizza, Benedict J. and Graham R. Leggatt (2017) Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients. PLoS One, 12 4: e0175755.1-e0175755.13. doi:10.1371/journal.pone.0175755


Author Linedale, Richard
Schmidt, Campbell
King, Brigid T.
Ganko, Annabelle G.
Simpson, Fiona
Panizza, Benedict J.
Graham R. Leggatt
Title Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2017-04-19
Year available 2017
Sub-type Article (original research)
DOI 10.1371/journal.pone.0175755
Open Access Status DOI
Volume 12
Issue 4
Start page e0175755.1
End page e0175755.13
Total pages 13
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
1100 Agricultural and Biological Sciences
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.
Formatted 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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 2013003030
Institutional Status UQ

 
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Created: Fri, 21 Apr 2017, 11:06:13 EST by Dr Graham Leggatt on behalf of UQ Diamantina Institute