Erin M Dickey, Anna Bianchi, Haleh Amirian, Peter J Hosein, Denise Faustman, Roberta Brambilla, Jashodeep Datta
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引用次数: 0
摘要
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。
Transmembrane TNF-TNFR2 signaling as a critical immunoregulatory node in pancreatic cancer.
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.
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.