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:Immunological effects of radiopharmaceutical therapy.
Immunological effects of radiopharmaceutical therapy.
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放射治疗(RT)是超过半数癌症患者所采用的癌症治疗支柱。临床上,RT主要以外部束放射治疗(EBRT)的形式实施。然而,EBRT在转移性病变中的适用范围有限,因为需要照射所有疾病部位。这种局限性归因于大范围EBRT野导致的放射诱导毒性,例如骨髓和血液学毒性。放射性药物治疗(RPT)已成为EBRT的替代方案,用于照射所有转移性疾病部位。虽然RPT可以减轻肿瘤负荷,但它也可能影响免疫系统和抗肿瘤免疫。理解这些效应对于预测和管理治疗相关的血液学毒性,以及优化其与其他治疗方式(如免疫治疗)的整合至关重要。
在此,我们综述基于α粒子和β粒子发射体的RPT对多种免疫细胞系的免疫调节效应,如CD8+和CD4+ T细胞、自然杀伤(NK)细胞和调节性T(Treg)细胞。
我们简要讨论基于俄歇电子发射体(AEE)的RPT,最后,我们重点介绍RPT与免疫检查点抑制剂的联合,这可能为转移性癌症患者提供潜在的治疗协同作用。
Radiation therapy (RT) is a pillar of cancer therapy used by more than half of all cancer patients. Clinically, RT is mostly delivered as external beam radiation therapy (EBRT).
However, the scope of EBRT is limited in the metastatic setting, where all sites of disease need to be irradiated. Such a limitation is attributed to radiation-induced toxicities, for example on bone marrow and hematologic toxicities, resulting from a large EBRT field. Radiopharmaceutical therapy (RPT) has emerged as an alternative to EBRT for the irradiation of all sites of metastatic disease.
While RPT can reduce tumor burden, it can also impact the immune system and anti-tumor immunity. Understanding these effects is crucial for predicting and managing treatment-related hematological toxicities and optimizing their integration with other therapeutic modalities, such as immunotherapies.
Here, we review the immunomodulatory effects of α- and β-particle emitter-based RPT on various immune cell lines, such as CD8+ and CD4+ T cells, natural killer (NK) cells, and regulatory T (Treg) cells.
We briefly discuss Auger electron-emitter (AEE)-based RPT, and finally, we highlight the combination of RPT with immune checkpoint inhibitors, which may offer potential therapeutic synergies for patients with metastatic cancers.
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