RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Targeting Neoantigens in Pancreatic Ductal Adenocarcinoma.
Targeting Neoantigens in Pancreatic Ductal Adenocarcinoma.
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胰腺导管腺癌(PDAC)是胰腺癌最常见的类型,目前是美国仅次于肺癌和结肠癌的第三大癌症相关死亡原因。预计到2030年,PDAC将成为第二大癌症相关死亡原因。晚期诊断是死亡率较高和手术后预后较差的根本原因。对化疗和免疫治疗的耐药导致手术后复发和预后不良。新抗原负荷和CD8+ T细胞浸润与PDAC的临床结局相关,而新抗原反应性TIL(肿瘤浸润淋巴细胞)的缺乏可能是免疫治疗耐药的根本原因。这表明需要识别额外的新抗原以及针对这些新抗原的疗法,以改善PDAC的临床结局。在这篇综述中,我们重点描述PDAC的病理生理学、当前治疗策略和治疗耐药,随后讨论PDAC中靶向新抗原的必要性。
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is currently the third leading cause of cancer-related death in the United States after lung and colon cancer. PDAC is estimated to be the second leading cause of cancer-related death by 2030. The diagnosis at a late stage is the underlying cause for higher mortality and poor prognosis after surgery. Treatment resistance to chemotherapy and immunotherapy results in recurrence after surgery and poor prognosis.
Neoantigen burden and CD8+ T-cell infiltration are associated with clinical outcomes in PDAC and paucity of neoantigen-reactive tumor-infiltrating lymphocytes may be the underlying cause for treatment resistance for immunotherapy. This suggests a need to identify additional neoantigens and therapies targeting these neoantigens to improve clinical outcomes in PDAC. In this review, we focus on describing the pathophysiology, current treatment strategies, and treatment resistance in PDAC followed by the need to target neoantigens in PDAC.
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