通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
我们的研究结果定义了一个精准溶瘤平台,该平台能够解除TAM介导的免疫抑制,同时增强适应性免疫,为癌症免疫治疗提供了一条有前景的转化途径。
英文原题:Therapeutic Strategies for Hepatocellular Carcinoma: Current Advances and Future Perspectives.
Therapeutic Strategies for Hepatocellular Carcinoma: Current Advances and Future Perspectives.
肝细胞癌(HCC)约占原发性肝癌的90%,并且仍然是全球癌症相关死亡的主要原因。
肝细胞癌(HCC)约占原发性肝癌的90%,仍是全球癌症相关死亡的主要原因之一。HCC的治疗面临重大挑战,原因在于其显著的分子异质性、诊断时多属晚期,以及对传统和现代治疗手段的固有耐药性。此外,相对较低的肿瘤突变负荷以及深度免疫抑制性肿瘤微环境(TME)的存在,显著限制了免疫治疗的疗效,尤其是在疾病晚期。近年来,新型免疫治疗策略——包括免疫检查点阻断(ICB)、溶瘤病毒治疗以及基因工程免疫细胞治疗——已引起广泛关注。然而,持久的临床缓解和总生存期的实质性改善仍然有限,凸显了在HCC中实现有效免疫控制的复杂性。新出现的证据表明,合理的联合免疫治疗策略可能通过克服免疫耐药机制提供新的治疗机会。在本综述中,我们全面概述了当前HCC的治疗策略,特别着重于免疫治疗方法。我们讨论了从诊断到治疗耐药的常见临床挑战,批判性评估了关键临床试验结果,并指出了旨在提高治疗疗效和长期疾病控制的未来方向。
Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers and remains a leading cause of cancer-related mortality worldwide. The management of HCC poses a major therapeutic challenge due to its pronounced molecular heterogeneity, frequent late-stage diagnosis, and intrinsic resistance to both conventional and modern therapeutic modalities. Furthermore, the relatively low tumor mutational burden and the presence of a profoundly immunosuppressive tumor microenvironment (TME) substantially limit the efficacy of immune-based interventions, particularly in advanced disease stages. In recent years, novel immunotherapeutic approaches-including immune checkpoint blockade (ICB), oncolytic virus therapy, and genetically engineered immune cell-based therapies-have garnered significant attention. Nevertheless, durable clinical responses and meaningful improvements in overall survival remain limited, underscoring the complexity of achieving effective immune control in HCC. Emerging evidence suggests that rational combination immunotherapy strategies may offer new therapeutic opportunities by overcoming immune resistance mechanisms. In this review, we provide a comprehensive overview of current therapeutic strategies for HCC, with particular emphasis on immunotherapeutic approaches. We discuss common clinical challenges spanning diagnosis to treatment resistance, critically evaluate key clinical trial outcomes, and highlight future directions aimed at improving therapeutic efficacy and long-term disease control.
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