التفاصيل البيبلوغرافية
| العنوان: |
High numbers of activated helper T cells are associated with better clinical outcome in early stage vulvar cancer, irrespective of HPV or p53 status |
| المؤلفون: |
Kim E. Kortekaas, Saskia J. Santegoets, Ziena Abdulrahman, Vanessa J. van Ham, Marij van der Tol, Ilina Ehsan, Helena C. van Doorn, Tjalling Bosse, Mariëtte I. E. van Poelgeest, Sjoerd H. van der Burg |
| المصدر: |
Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-13 (2019) |
| بيانات النشر: |
BMJ Publishing Group, 2019. |
| سنة النشر: |
2019 |
| المجموعة: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: |
Vulvar cancer, Tumor microenvironment, Immunotherapy, T cells, PD-1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: |
Abstract Background Vulvar squamous cell carcinoma (VSCC) has been suggested to consist of three subtypes; HPV-positive, HPV-negative mutated TP53 or HPV-negative TP53 wildtype, with different clinical courses. To analyze the immune infiltrate in these molecular subtypes and its impact on clinical outcome, an in-depth study of the tumor immune microenvironment was performed. Methods Sixty-five patients with invasive VSCC matched for age, FIGO stage and treatment modality, were grouped according to the presence of HPV and p53 protein expression status. Archived tissues were analyzed for intraepithelial and stromal expression of CD3, CD8, Foxp3, PD-1, and pan-keratin in randomly selected areas using immunofluorescence. Additional phenotyping of T cells was performed ex-vivo on VSCC (n = 14) and blood samples by flow cytometry. Healthy vulvar samples and blood served as controls. Results Based on T-cell infiltration patterns about half of the VSCC were classified as inflamed or altered-excluded while one-third was immune-deserted. High intraepithelial helper T cell infiltration was observed in 78% of the HPV-induced VSCC, 60% of the HPVnegVSCC/p53wildtype and 40% of the HPVnegVSCC with abnormal p53 expression. A high intraepithelial infiltration with activated (CD3+PD-1+), specifically helper T cells (CD3+CD8−Foxp3−), was associated with a longer recurrence-free period and overall survival, irrespective of HPV and p53 status. Flow cytometry confirmed the tumor-specific presence of activated (CD4+PD-1++CD161−CD38+HLA-DR+ and CD8+CD103+CD161−NKG2A+/−PD1++CD38++HLA-DR+) effector memory T cells. Conclusion This is the first study demonstrating an association between intraepithelial T cells and clinical outcome in VSCC. Our data suggest that abnormal p53 expressing VSCCs mostly are cold tumors whereas HPV-driven VSCCs are strongly T-cell infiltrated. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2051-1426 |
| Relation: |
http://link.springer.com/article/10.1186/s40425-019-0712-z; https://doaj.org/toc/2051-1426 |
| DOI: |
10.1186/s40425-019-0712-z |
| URL الوصول: |
https://doaj.org/article/278594b3dd424428aaf79480406433b9 |
| رقم الانضمام: |
edsdoj.278594b3dd424428aaf79480406433b9 |
| قاعدة البيانات: |
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