干旱区生态环境知识资源中心(Arid): Article Long-lasting mRNA-encoded interleukin-2 restores CD8+T cell neoantigen immunity in MHC class I-deficient cancers

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DOI	10.1016/j.ccell.2024.02.013
	Article Long-lasting mRNA-encoded interleukin-2 restores CD8+T cell neoantigen immunity in MHC class I-deficient cancers
	Beck, Jan D.; Diken, Mustafa; Suchan, Martin; Streuber, Michael; Diken, Elif; Kolb, Laura; Allnoch, Lisa; Vascotto, Fulvia; Peters, Daniel; Beissert, Tim; Akilli-Oeztuerk, Oezlem; Tuereci, Oezlem; Kreiter, Sebastian; Vormehr, Mathias; Sahin, Ugur
通讯作者	Vormehr, M
来源期刊	CANCER CELL
ISSN	1535-6108
EISSN	1878-3686
出版年	2024
卷号	42 期号:4
英文摘要	Major histocompatibility complex (MHC) class I antigen presentation deficiency is a common cancer immune escape mechanism, but the mechanistic implications and potential strategies to address this challenge remain poorly understood. Studying b2-microglobulin (B2M) deficient mouse tumor models, we find that MHC class I loss leads to a substantial immune desertification of the tumor microenvironment (TME) and broad resistance to immune-, chemo-, and radiotherapy. We show that treatment with long-lasting mRNAencoded interleukin-2 (IL -2) restores an immune cell infiltrated, IFNg-promoted, highly proinflammatory TME signature, and when combined with a tumor -targeting monoclonal antibody (mAB), can overcome therapeutic resistance. Unexpectedly, the effectiveness of this treatment is driven by IFNg-releasing CD8 + T cells that recognize neoantigens cross -presented by TME-resident activated macrophages. These macrophages acquire augmented antigen presentation proficiency and other M1 -phenotype -associated features under IL -2 treatment. Our findings highlight the importance of restoring neoantigen-specific immune responses in the treatment of cancers with MHC class I deficiencies.
类型	Article
语种	英语
开放获取类型	Green Submitted
收录类别	SCI-E
WOS记录号	WOS:001228472500003
WOS关键词	PD-1 BLOCKADE ; IFN-GAMMA ; RECOMBINANT INTERLEUKIN-2 ; ACQUIRED-RESISTANCE ; DENDRITIC CELLS ; TUMOR-CELLS ; MECHANISM ; RADIATION ; ELIMINATION ; EFFICIENCY
WOS类目	Oncology ; Cell Biology
WOS研究方向	Oncology ; Cell Biology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/403103
推荐引用方式 GB/T 7714	Beck, Jan D.,Diken, Mustafa,Suchan, Martin,et al. Article Long-lasting mRNA-encoded interleukin-2 restores CD8+T cell neoantigen immunity in MHC class I-deficient cancers[J],2024,42(4).
APA	Beck, Jan D..,Diken, Mustafa.,Suchan, Martin.,Streuber, Michael.,Diken, Elif.,...&Sahin, Ugur.(2024).Article Long-lasting mRNA-encoded interleukin-2 restores CD8+T cell neoantigen immunity in MHC class I-deficient cancers.CANCER CELL,42(4).
MLA	Beck, Jan D.,et al."Article Long-lasting mRNA-encoded interleukin-2 restores CD8+T cell neoantigen immunity in MHC class I-deficient cancers".CANCER CELL 42.4(2024).