Transmembrane TNF-TNFR2 signaling as a critical immunoregulatory node in pancreatic cancer.

IF 6.5 2区 医学 Q1 IMMUNOLOGY Oncoimmunology Pub Date : 2024-03-12 eCollection Date: 2024-01-01 DOI:10.1080/2162402X.2024.2326694
Erin M Dickey, Anna Bianchi, Haleh Amirian, Peter J Hosein, Denise Faustman, Roberta Brambilla, Jashodeep Datta
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Abstract

Pancreatic cancer is characterized by extreme therapeutic resistance. In pancreatic cancers harboring high-risk genomes, we describe that cancer cell-neutrophil signaling circuitry provokes neutrophil-derived transmembrane (tm)TNF-TNFR2 interactions that dictate inflammatory polarization in cancer-associated fibroblasts and T-cell dysfunction - two hallmarks of therapeutic resistance. Targeting tmTNF-TNFR2 signaling may sensitize pancreatic cancer to chemo±immunotherapy.

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跨膜 TNF-TNFR2 信号是胰腺癌的关键免疫调节节点。
胰腺癌具有极强的抗药性。在携带高风险基因组的胰腺癌中,我们描述了癌细胞-中性粒细胞信号传导回路引发了中性粒细胞衍生的跨膜(tm)TNF-TNFR2 相互作用,这种作用决定了癌症相关成纤维细胞的炎症极化和 T 细胞功能障碍--这是治疗耐药性的两个标志。以tmTNF-TNFR2信号为靶点可使胰腺癌对化疗和免疫疗法敏感。
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来源期刊
Oncoimmunology
Oncoimmunology ONCOLOGYIMMUNOLOGY-IMMUNOLOGY
CiteScore
12.50
自引率
2.80%
发文量
276
审稿时长
24 weeks
期刊介绍: OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy. As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology. The journal covers a wide range of topics, including: -Basic and translational studies in immunology of both solid and hematological malignancies -Inflammation, innate and acquired immune responses against cancer -Mechanisms of cancer immunoediting and immune evasion -Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells -Immunological effects of conventional anticancer therapies.
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