Article ; Online: Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.
PloS one
2017 Volume 12, Issue 4, Page(s) e0175755
Abstract: ... to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using ... infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 ... we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell ...
| 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. |
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| MeSH term(s) | Aged ; Aged, 80 and over ; B7-H1 Antigen/genetics ; B7-H1 Antigen/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; CTLA-4 Antigen/genetics ; CTLA-4 Antigen/immunology ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/immunology ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/surgery ; Cohort Studies ; Cranial Nerves/immunology ; Cranial Nerves/pathology ; Cranial Nerves/surgery ; Female ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/pathology ; Head and Neck Neoplasms/surgery ; Hepatitis A Virus Cellular Receptor 2/genetics ; Hepatitis A Virus Cellular Receptor 2/immunology ; Humans ; Killer Cells, Natural/immunology ; Killer Cells, Natural/pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/immunology ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/surgery ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/immunology ; Skin Neoplasms/genetics ; Skin Neoplasms/immunology ; Skin Neoplasms/pathology ; Skin Neoplasms/surgery |
| Chemical Substances | B7-H1 Antigen ; CD274 protein, human ; CTLA-4 Antigen ; HAVCR2 protein, human ; Hepatitis A Virus Cellular Receptor 2 ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor |
| Language | English |
| Publishing date | 2017 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 1932-6203 |
| ISSN (online) | 1932-6203 |
| DOI | 10.1371/journal.pone.0175755 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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