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:Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapy.
Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapy.
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肺癌,主要是非小细胞肺癌(NSCLC),仍然是全球癌症相关发病率和死亡率的主要驱动因素。尽管手术、放疗、化疗和靶向治疗取得了进展,晚期NSCLC的预后仍然较差。肿瘤微环境(TME)对治疗反应具有关键影响。在TME中,免疫细胞如T和B淋巴细胞、树突状细胞、髓源性抑制细胞、肿瘤相关巨噬细胞、中性粒细胞和NK 细胞既可驱动促肿瘤过程,也可驱动抗肿瘤过程。本综述整合了它们在NSCLC中的分类、表型可塑性和作用,重点介绍了关键的临床前和临床证据,同时讨论了发病机制、预后意义和治疗潜力。我们还总结了目前晚期NSCLC的免疫治疗策略,包括免疫检查点抑制剂单药或联合化疗、抗血管生成药物或其他检查点抑制剂的一线或二线方案,以及未来方向。通过阐明NSCLC免疫微环境与新兴免疫治疗之间的相互作用,本综述强调了新型联合方案和稳健预测生物标志物的必要性,以改善晚期NSCLC的临床结局并延长生存期。
Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a principal driver of cancer-related morbidity and mortality worldwide. Despite advancements in surgery, radiotherapy, chemotherapy, and targeted treatments, outcomes remain poor in advanced NSCLC. The tumor microenvironment (TME) exerts a critical influence on therapy responses.
Within the TME, immune cells such as T and B lymphocytes, dendritic cells, myeloid-derived suppressor cells, tumor-associated macrophages, neutrophils, and natural killer cells can drive both pro- and anti-tumor processes. This review integrates their classification, phenotypic plasticity, and roles in NSCLC, highlighting key preclinical and clinical evidence while discussing pathogenesis, prognostic significance, and therapeutic potential.
We also summarize the current immunotherapeutic strategies for advanced NSCLC, including first- or second-line regimens with immune checkpoint inhibitors alone or combined with chemotherapy, anti-angiogenic agents, or additional checkpoint inhibitors, and future directions. By elucidating the interplay between the NSCLC immune microenvironment and emerging immunotherapies, this review emphasizes the need for novel combination regimens and robust predictive biomarkers to improve clinical outcomes and extend survival in advanced NSCLC.
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