干旱区生态环境知识资源中心(Arid): Immune profiling and immunotherapeutic targets in pancreatic cancer

Arid

DOI	10.21037/atm-20-1076
	Immune profiling and immunotherapeutic targets in pancreatic cancer
	Lenzo, Felicia L.; Kato, Shumei; Pabla, Sarabjot; DePietro, Paul; Nesline, Mary K.; Conroy, Jeffrey M.; Burgher, Blake; Glenn, Sean T.; Kuvshinoff, Boris; Kurzrock, Razelle; Morrison, Carl
通讯作者	Morrison, C (corresponding author), Roswell Park Comprehens Canc Ctr, Elm & Carlton St, Buffalo, NY 14263 USA.
来源期刊	ANNALS OF TRANSLATIONAL MEDICINE
ISSN	2305-5839
EISSN	2305-5847
出版年	2021
卷号	9 期号:2
英文摘要	Background: Immunotherapeutic approaches for pancreatic ductal adenocarcinoma (PDAC) are less successful as compared to many other tumor types. In this study, comprehensive immune profiling was performed in order to identify novel, potentially actionable targets for immunotherapy. Methods: Formalin-fixed paraffin embedded (FFPE) specimens from 68 patients were evaluated for expression of 395 immune-related markers (RNA-seq), mutational burden by complete exon sequencing of 409 genes, PD-L1 expression by immunohistochemistry (IHC), pattern of tumor infiltrating lymphocytes (TILs) infiltration by CD8 IHC, and PD-L1/L2 copy number by fluorescent in situ hybridization (FISH). Results: The seven classes of actionable genes capturing myeloid immunosuppression, metabolic immunosuppression, alternative checkpoint blockade, CTLA-4 immune checkpoint, immune infiltrate, and programmed cell death 1 (PD-1) axis immune checkpoint, discerned 5 unique clinically relevant immunosuppression expression profiles (from most to least common): (I) combined myeloid and metabolic immunosuppression [affecting 25 of 68 patients (36.8%)], (II) multiple immunosuppressive mechanisms (29.4%), (III) PD-L1 positive (20.6%), (IV) highly inflamed PD-L1 negative (10.3%); and (V) immune desert (2.9%). The Wilcoxon rank-sum test was used to compare the PDAC cohort with a comparison cohort (n=1,416 patients) for the mean expressions of the 409 genes evaluated. Multiple genes including TIM3, VISTA, CCL2, CCR2, TGFB1, CD73, and CD39 had significantly higher mean expression versus the comparison cohort, while three genes (LAG3, GITR, CD38) had significantly lower mean expression. Conclusions: This study demonstrates that a clinically relevant unique profile of immune markers can be identified in PDAC and be used as a roadmap for personalized immunotherapeutic decision-making strategies.
英文关键词	Precision immunotherapy PD-L1 immune suppression immune activation checkpoint inhibitors
类型	Article
语种	英语
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000617883600024
WOS关键词	TUMOR ; EXPRESSION ; RESPONSES ; SUBTYPES ; ADENOCARCINOMA ; GEMCITABINE ; FOLFIRINOX ; BIOMARKER ; ANTIBODY ; CELLS
WOS类目	Oncology ; Medicine, Research & Experimental
WOS研究方向	Oncology ; Research & Experimental Medicine
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/349470
作者单位	[Lenzo, Felicia L.; Pabla, Sarabjot; DePietro, Paul; Nesline, Mary K.; Conroy, Jeffrey M.; Burgher, Blake; Glenn, Sean T.; Morrison, Carl] OmniSeq Inc, Buffalo, NY USA; [Kato, Shumei; Kurzrock, Razelle] Moores Canc Ctr, Ctr Personalized Canc Therapy, La Jolla, CA USA; [Conroy, Jeffrey M.; Glenn, Sean T.; Morrison, Carl] Roswell Park Comprehens Canc Ctr, Ctr Personalized Med, Buffalo, NY 14263 USA; [Glenn, Sean T.] Roswell Park Comprehens Canc Ctr, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA; [Kuvshinoff, Boris] Roswell Park Comprehens Canc Ctr, Dept Surg, Buffalo, NY 14263 USA; [Morrison, Carl] Roswell Park Comprehens Canc Ctr, Dept Pathol, Buffalo, NY 14263 USA; [Morrison, Carl] Roswell Park Comprehens Canc Ctr, Canc Genet & Genom, Buffalo, NY 14263 USA
推荐引用方式 GB/T 7714	Lenzo, Felicia L.,Kato, Shumei,Pabla, Sarabjot,et al. Immune profiling and immunotherapeutic targets in pancreatic cancer[J],2021,9(2).
APA	Lenzo, Felicia L..,Kato, Shumei.,Pabla, Sarabjot.,DePietro, Paul.,Nesline, Mary K..,...&Morrison, Carl.(2021).Immune profiling and immunotherapeutic targets in pancreatic cancer.ANNALS OF TRANSLATIONAL MEDICINE,9(2).
MLA	Lenzo, Felicia L.,et al."Immune profiling and immunotherapeutic targets in pancreatic cancer".ANNALS OF TRANSLATIONAL MEDICINE 9.2(2021).