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:Understanding the immune response and the current landscape of immunotherapy in pancreatic cancer.
Understanding the immune response and the current landscape of immunotherapy in pancreatic cancer.
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胰腺导管腺癌(PDAC)是一种具有高致死率的侵袭性肿瘤。即使采用手术、放疗、化疗以及其他局部区域或全身性治疗,PDAC 的生存率仍然很低,且在过去几十年中未有显著改变。在设计该疾病的新型治疗方法时,需要考虑 PDAC 微环境的特殊特征及其复杂的免疫逃逸机制。PDAC 的特征是慢性炎症,伴有高比例的肿瘤相关巨噬细胞和髓源性抑制细胞,以及低比例的NK 细胞和效应 T 细胞。胰腺微环境是一种纤维化、微血管化的基质,将肿瘤与全身血管化隔离。免疫治疗是一种在某些实体瘤中已显示出有效性的新方法,但在胰腺癌中未能显示出任何改变实践的结果,例外的是具有错配修复缺陷和高肿瘤突变负荷的 PDAC,这些患者在接受免疫治疗时显示出延长的生存率。目前,众多临床试验正在尝试评估免疫治疗策略在 PDAC 中的疗效,包括免疫检查点抑制剂、癌症疫苗和过继细胞转移,单独使用或与其他免疫治疗药物、放化疗及其他靶向治疗联合使用。对免疫反应的深入理解将有助于开发新的治疗策略,从而改善 PDAC 患者的临床结局。
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with high lethality. Even with surgery, radiotherapy, chemotherapy, and other locoregional or systemic therapies, the survival rates for PDAC are low and have not significantly changed in the past decades. The special characteristics of the PDAC's microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this disease. PDAC is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T cells. The pancreatic microenvironment is a fibrotic, microvascularized stroma that isolates the tumor from systemic vascularization.
Immunotherapy, a novel approach that has demonstrated effectiveness in certain solid tumors, has failed to show any practice-changing results in pancreatic cancer, with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden, which show prolonged survival rates with immunotherapy.
Currently, numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell transfer, alone or in combination with other immunotherapeutic agents, chemoradiotherapy, and other targeted therapies. A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.
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