ArticlePloS one2017
Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Immunotherapy and Radiation for Clinical Perineural Invasion in Cutaneous Squamous Cell Carcinoma.Cancers · 2025Review
- Review
- Cancer neuroscience in head and neck: interactions, modulation, and therapeutic strategies.Molecular cancer · 2025Review
- Significance and mechanisms of perineural invasion in malignant tumors.Frontiers in oncology · 2025Review
- Review
- CD8/PD-L1 immunohistochemical reactivity and gene alterations in cutaneous squamous cell carcinoma.PloS one · 2023Article
- Exhaustion of CD8Frontiers in immunology · 2023Article
- Review
- Monitoring Pre- and Post-Operative Immune Alterations in Patients With Locoregional Colorectal Cancer Who Underwent Laparoscopy by Single-Cell Mass Cytometry.Frontiers in immunology · 2022Article
- The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities.Frontiers in cell and developmental biology · 2021Review
- Review
- Review
- Looking past PD-L1: expression of immune checkpoint TIM-3 and its ligand galectin-9 in cervical and vulvar squamous neoplasia.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Soluble PD-1: Predictive, Prognostic, and Therapeutic Value for Cancer Immunotherapy.Frontiers in immunology · 2020Review
- NK Cell-Based Immune Checkpoint Inhibition.Frontiers in immunology · 2020Review
- Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer.Frontiers in oncology · 2020Review
- PD-L1/PD1 Expression, Composition of Tumor-Associated Immune Infiltrate, and HPV Status in Conjunctival Squamous Cell Carcinoma.Investigative ophthalmology & visual science · 2019Article
- The Role of the Immune System in Cutaneous Squamous Cell Carcinoma.International journal of molecular sciences · 2019Review
- CXCR4 and PD-1 Expression in Head and Neck Cancer with Perineural Spread.Journal of neurological surgery. Part B, Skull base · 2019Article
- The Rise of NK Cell Checkpoints as Promising Therapeutic Targets in Cancer Immunotherapy.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.