一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Advances in the Lung Cancer Immunotherapy Approaches.
Advances in the Lung Cancer Immunotherapy Approaches.
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尽管在理解LC进展、风险、免疫控制和治疗选择方面取得了进展,它仍然是癌症相关死亡的主要原因。LC细胞具有非常低且异质的抗原性,这使它们能够通过教育细胞毒性淋巴细胞(CTLs)、TIL(肿瘤浸润淋巴细胞)(TILs)、调节性T细胞(Treg)、免疫检查点抑制剂(ICIs)和髓源性抑制细胞(MDSCs),被动逃避免疫系统的抗癌防御。尽管ICIs是一线治疗、巩固治疗、辅助治疗以及涉及传统疗法的其他联合治疗的重要候选者,但对新的预测性免疫治疗生物标志物的需求仍然存在。
此外,初始反应后ICI诱导的耐药性使得寻找和利用新靶点以从免疫治疗中获得更大益处变得至关重要。由于ICIs、肿瘤突变负荷(TMB)和微卫星不稳定性(MSI)并非理想的LC预测标志物,考虑肿瘤、基质及其他方面的免疫系统多参数分析可能是面向未来的预测标志物。在免疫治疗方法中,通过适当的辅助药物进行最佳患者选择仍需修订。
在此,我们总结了LC免疫治疗方法的进展及其临床和临床前试验,考虑癌症模型和疫苗,以及利用免疫学预测癌症患者免疫治疗效果的潜力,并探讨未来方向的观点。
我们得出结论,肺癌治疗领域可以从联合策略的使用中受益,但需要理解其局限性和改进之处。
Despite the progress in the comprehension of LC progression, risk, immunologic control, and treatment choices, it is still the primary cause of cancer-related death. LC cells possess a very low and heterogeneous antigenicity, which allows them to passively evade the anticancer defense of the immune system by educating cytotoxic lymphocytes (CTLs), tumor-infiltrating lymphocytes (TILs), regulatory T cells (Treg), immune checkpoint inhibitors (ICIs), and myeloid-derived suppressor cells (MDSCs).
Though ICIs are an important candidate in first-line therapy, consolidation therapy, adjuvant therapy, and other combination therapies involving traditional therapies, the need for new predictive immunotherapy biomarkers remains.
Furthermore, ICI-induced resistance after an initial response makes it vital to seek and exploit new targets to benefit greatly from immunotherapy. As ICIs, tumor mutation burden (TMB), and microsatellite instability (MSI) are not ideal LC predictive markers, a multi-parameter analysis of the immune system considering tumor, stroma, and beyond can be the future-oriented predictive marker. The optimal patient selection with a proper adjuvant agent in immunotherapy approaches needs to be still revised.
Here, we summarize advances in LC immunotherapy approaches with their clinical and preclinical trials considering cancer models and vaccines and the potential of employing immunology to predict immunotherapy effectiveness in cancer patients and address the viewpoints on future directions.
We conclude that the field of lung cancer therapeutics can benefit from the use of combination strategies but with comprehension of their limitations and improvements.
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