决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Immunotherapy for virus-related hepatocellular carcinoma: recent progress and future directions.
Immunotherapy for virus-related hepatocellular carcinoma: recent progress and future directions.
免疫疗法为病毒相关肝细胞癌(HCC)患者带来了新希望,但在应答异质性、耐药和毒性方面仍存在挑战。
背景:肝细胞癌(HCC)是全球癌症相关死亡的主要原因之一,乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染仍是主要病因。慢性病毒感染不仅驱动癌变,还会重塑肝脏免疫微环境,深刻影响免疫治疗的疗效和安全性。 近期进展:免疫检查点抑制剂(ICI)已改变晚期HCC的系统治疗格局,靶向PD-1/PD-L1的药物显示出临床获益。ICI联合抗血管生成疗法、多激酶抑制剂或局部区域治疗等策略已显示协同疗效,并在某些治疗情境中成为标准治疗。对于病毒相关HCC,抗病毒治疗可改善免疫反应并降低HBV再激活等风险,凸显综合管理的必要性。 未来展望:新兴治疗方法包括新一代免疫检查点(如TIM-3、LAG-3、TIGIT)、双特异性抗体、细胞疗法(CAR-T、TCR-T、TIL(肿瘤浸润淋巴细胞)及靶向病毒或肿瘤相关抗原的肿瘤疫苗。循环肿瘤DNA、免疫特征和微生物组调节等生物标志物发现进展,有望指导个体化治疗。整合多组学与临床数据将进一步完善患者筛选并优化治疗顺序。 结论:免疫治疗为病毒相关HCC患者带来新希望,但应答异质性、耐药和毒性等挑战仍然存在。必须采用个体化策略,将免疫治疗与有效抗病毒管理及基于生物标志物的患者筛选相结合。持续开展病毒—免疫—肿瘤相互作用的转化及临床研究,将有助于实现更安全、有效且持久的治疗结局,最终使HCC更易于控制。
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remaining the predominant etiological factors. Chronic viral infection not only drives carcinogenesis but also reshapes the hepatic immune microenvironment, profoundly influencing the efficacy and safety of immunotherapy. RECENT ADVANCES: Immune checkpoint inhibitors (ICIs) have revolutionized systemic therapy for advanced HCC, with agents targeting PD-1/PD-L1 demonstrating clinical benefit. Combination strategies - such as ICIs with anti-angiogenic therapies, multikinase inhibitors, or locoregional treatments - have shown synergistic efficacy and are now standard of care in certain settings. For virus-related HCC, antiviral therapy improves immune responsiveness and reduces risks such as HBV reactivation, underscoring the need for integrated management. FUTURE PERSPECTIVES: Emerging therapeutic approaches include next-generation immune checkpoints (e.g. TIM-3, LAG-3, TIGIT), bispecific antibodies, cellular therapies (CAR-T, TCR-T, TILs), and tumor vaccines targeting viral or tumor-associated antigens. Advances in biomarker discovery, including circulating tumor DNA, immune signatures, and microbiome modulation, are expected to guide personalized treatment. Integration of multi-omics and clinical data will further refine patient selection and optimize treatment sequencing. CONCLUSION: Immunotherapy offers new hope for patients with virus-related HCC, but challenges remain in response heterogeneity, resistance, and toxicity. Individualized strategies that combine immunotherapy with effective antiviral management and biomarker-|guided patient selection are essential. Continued translational and clinical research into virus-immune-tumor interactions will enable safer, more effective, and more durable treatment outcomes, ultimately transforming HCC into a more manageable disease.
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