干旱区生态环境知识资源中心(Arid): High numbers of activated helper T cells are associated with better clinical outcome in early stage vulvar cancer, irrespective of HPV or p53 status

Arid

DOI	10.1186/s40425-019-0712-z
	High numbers of activated helper T cells are associated with better clinical outcome in early stage vulvar cancer, irrespective of HPV or p53 status
	Kortekaas, Kim E.1,3; Santegoets, Saskia J.3; Abdulrahman, Ziena 3; van Ham, Vanessa J.3; van der Tol, Marij 2; Ehsan, Ilina 3; van Doom, Helena C.4; Bosse, Tjalling 5; van Poelgeest, Mariette I. E.2; van der Burg, Sjoerd H.3
通讯作者	van der Burg, Sjoerd H.
来源期刊	JOURNAL FOR IMMUNOTHERAPY OF CANCER
ISSN	2051-1426
出版年	2019
卷号	7 期号:1
英文摘要	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.
英文关键词	Vulvar cancer Tumor microenvironment Immunotherapy T cells PD-1
类型	Article
语种	英语
国家	Netherlands
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000483765300001
WOS关键词	INTRAEPITHELIAL NEOPLASIA ; PROGNOSTIC-SIGNIFICANCE ; CARCINOMA ; EXPRESSION ; MICROENVIRONMENT ; IMMUNOTHERAPY ; INFILTRATION ; RECURRENCE ; IMIQUIMOD ; CONSENSUS
WOS类目	Oncology ; Immunology
WOS研究方向	Oncology ; Immunology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/216586
作者单位	1.Leiden Univ, Med Ctr, Oncode Inst, Dept Gynecol, POB 9600, NL-2300 RC Leiden, Netherlands; 2.Leiden Univ, Med Ctr, Dept Gynecol, POB 9600, NL-2300 RC Leiden, Netherlands; 3.Leiden Univ, Med Ctr, Oncode Inst, Dept Med Oncol, POB 9600, NL-2300 RC Leiden, Netherlands; 4.Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Gynecol Oncol, POB 2040, NL-2300 CA Rotterdam, Netherlands; 5.Leiden Univ, Med Ctr, Dept Pathol, POB 9600, NL-2300 RC Leiden, Netherlands
推荐引用方式 GB/T 7714	Kortekaas, Kim E.,Santegoets, Saskia J.,Abdulrahman, Ziena,et al. High numbers of activated helper T cells are associated with better clinical outcome in early stage vulvar cancer, irrespective of HPV or p53 status[J],2019,7(1).
APA	Kortekaas, Kim E..,Santegoets, Saskia J..,Abdulrahman, Ziena.,van Ham, Vanessa J..,van der Tol, Marij.,...&van der Burg, Sjoerd H..(2019).High numbers of activated helper T cells are associated with better clinical outcome in early stage vulvar cancer, irrespective of HPV or p53 status.JOURNAL FOR IMMUNOTHERAPY OF CANCER,7(1).
MLA	Kortekaas, Kim E.,et al."High numbers of activated helper T cells are associated with better clinical outcome in early stage vulvar cancer, irrespective of HPV or p53 status".JOURNAL FOR IMMUNOTHERAPY OF CANCER 7.1(2019).