干旱区生态环境知识资源中心(Arid): Primary vulvar squamous cell carcinomas with high T cell infiltration and active immune signaling are potential candidates for neoadjuvant PD-1/PD-L1 immunotherapy

Arid

DOI	10.1136/jitc-2021-003671
	Primary vulvar squamous cell carcinomas with high T cell infiltration and active immune signaling are potential candidates for neoadjuvant PD-1/PD-L1 immunotherapy
	Kortekaas, Kim E.; Santegoets, Saskia J.; Tas, Liselotte; Ehsan, Ilina; Charoentong, Pornpimol; van Doorn, Helena C.; van Poelgeest, Mariette I. E.; Mustafa, Dana A. M.; van der Burg, Sjoerd H.
通讯作者	van der Burg, SH (corresponding author), Leiden Univ, Oncode Inst, Dept Med Oncol, Med Ctr, Leiden, Netherlands.
来源期刊	JOURNAL FOR IMMUNOTHERAPY OF CANCER
EISSN	2051-1426
出版年	2021
卷号	9 期号:10
英文摘要	Background A profound insight into the immune landscape of vulvar squamous cell carcinoma (VSCC) is lacking. Here, an in-depth interrogation of T cell infiltration, local immune contexture, signaling pathways and checkpoint molecule expression was performed in early-stage and late-stage VSCC. Methods The type, location, and infiltration pattern of T cells were studied in 109 patients with primary VSCC FIGO stage I-III. RNA expression of genes involved in immune oncology and oncogenic signaling pathways was analyzed in 40 VSCC, matched for prognostic clinicopathological variables, analyzed for HPV and p53 status, and selected based on T cell infiltration. Results High intraepithelial infiltration with CD4 or CD8 T cells was associated with longer overall and recurrence-free survival and formed an independent prognostic factor, outperforming molecular subtype and stage of the disease. Strong T cell infiltrated VSCC displayed a coordinated immune response reflected by a positive association between T cells and different lymphocyte and myeloid cell subsets. The expression of genes involved in the migration of T cells and myeloid cells, T cell activation and costimulation, interferon (IFN)-gamma signaling, cytotoxicity and apoptosis was higher than in low infiltrated tumors. An active immune signaling profile was observed in all inflamed, part of the altered-excluded and not in altered-immunosuppressed or deserted VSCC. While several checkpoint molecules were overexpressed, only PD-L1 expression displayed discriminatory ability and clinical usefulness. High PD-L1 expression was detected in all inflamed and similar to 60% of the altered-excluded VSCC. Conclusion An active immune signaling profile is present in 35% of primary FIGO I-III VSCCs, suggesting potential responsiveness to neoadjuvant PD-1/PD-L1 immunotherapy.
类型	Article
语种	英语
开放获取类型	gold
收录类别	SCI-E
WOS记录号	WOS:000714174500002
WOS关键词	IFN-GAMMA ; CANCER ; MACROPHAGES ; CONTEXTURE ; EXPRESSION ; PROFILE ; TH1
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/2XILL650/368370
作者单位	[Kortekaas, Kim E.; Tas, Liselotte; van Poelgeest, Mariette I. E.] Leiden Univ, Dept Gynecol, Med Ctr, Leiden, Netherlands; [Santegoets, Saskia J.; Ehsan, Ilina; van der Burg, Sjoerd H.] Leiden Univ, Oncode Inst, Dept Med Oncol, Med Ctr, Leiden, Netherlands; [Charoentong, Pornpimol] Univ Hosp Heidelberg, Dept Med Oncol, German Canc Res Ctr DKFZ, Appl Tumor Immun, Heidelberg, Germany; [Charoentong, Pornpimol] Univ Hosp Heidelberg, Natl Ctr Tumor Dis, Appl Tumor Immun, German Canc Res Ctr DKFZ, Heidelberg, Germany; [van Doorn, Helena C.] Erasmus MC, Dept Gynecol, Rotterdam, Netherlands; [Mustafa, Dana A. M.] Erasmus MC, Dept Pathol, Rotterdam, Netherlands
推荐引用方式 GB/T 7714	Kortekaas, Kim E.,Santegoets, Saskia J.,Tas, Liselotte,et al. Primary vulvar squamous cell carcinomas with high T cell infiltration and active immune signaling are potential candidates for neoadjuvant PD-1/PD-L1 immunotherapy[J],2021,9(10).
APA	Kortekaas, Kim E..,Santegoets, Saskia J..,Tas, Liselotte.,Ehsan, Ilina.,Charoentong, Pornpimol.,...&van der Burg, Sjoerd H..(2021).Primary vulvar squamous cell carcinomas with high T cell infiltration and active immune signaling are potential candidates for neoadjuvant PD-1/PD-L1 immunotherapy.JOURNAL FOR IMMUNOTHERAPY OF CANCER,9(10).
MLA	Kortekaas, Kim E.,et al."Primary vulvar squamous cell carcinomas with high T cell infiltration and active immune signaling are potential candidates for neoadjuvant PD-1/PD-L1 immunotherapy".JOURNAL FOR IMMUNOTHERAPY OF CANCER 9.10(2021).