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:From Excision to Immunity: The Full Spectrum of Modern Melanoma Treatments.
From Excision to Immunity: The Full Spectrum of Modern Melanoma Treatments.
皮肤黑色素瘤是一种生物学上异质性强的恶性肿瘤。
皮肤黑色素瘤是一种生物学上异质性很强的恶性肿瘤。尽管近年来的治疗进展改善了生存率,但许多患者仍难以实现持久缓解。以分期适当切缘进行手术切除并选择性进行淋巴结分期,仍是根治性治疗管理的基石。相比之下,传统细胞毒性化疗由于疗效有限且毒性显著,目前仅发挥有限的、主要为姑息性的作用。BRAF/MEK抑制剂靶向治疗改善了BRAF V600突变型黑色素瘤患者的结局,可实现快速肿瘤消退并带来有意义的生存获益。然而,长期疾病控制常因适应性耐药而受损,这种耐药通常由MAPK通路再激活或代偿性PI3K/AKT信号驱动。与此同时,靶向PD-1、CTLA-4及新兴通路的免疫检查点抑制剂重塑了各疾病阶段的治疗格局,使患者能够获得深度且有时持久的缓解。尽管取得了这些进展,原发性和获得性耐药,以及急性和慢性免疫相关毒性,仍构成重大的临床挑战。当前的治疗策略聚焦于靶向治疗、检查点阻断、基于IL-2的方法、溶瘤病毒以及过继性细胞疗法(如TIL(肿瘤浸润淋巴细胞)的合理联合,以增强缓解深度和持久性。然而,这些强化方案带来更高的毒性风险,凸显了改进患者筛选和监测的必要性。总体而言,新出现的证据支持向优化治疗序贯、应答适应性手术策略以及生物标志物指导的个体化治疗转变,以在最大化临床获益的同时尽量减少毒性。
Cutaneous Melanoma is a biologically heterogeneous malignancy. Although recent therapeutic advances have improved survival, durable remissions remain elusive for many patients. Surgical excision with stage-appropriate margins and selective nodal staging remains the cornerstone of curative-intent management. In contrast, conventional cytotoxic chemotherapy now plays a limited, largely palliative role given its modest efficacy and substantial toxicity. Targeted therapy with BRAF/MEK inhibitors has improved outcomes in patients with BRAF V600-mutant melanoma, resulting in rapid tumor regression and meaningful survival benefits. However, long-term disease control is frequently compromised by adaptive resistance, commonly driven by MAPK pathway reactivation or compensatory PI3K/AKT signaling. In parallel, immune checkpoint inhibitors targeting PD-1, CTLA-4, and emerging pathways have reshaped treatment across disease stages, enabling deep and sometimes durable responses. Despite this progress, primary and acquired resistance, as well as acute and chronic immune-related toxicities, continue to pose significant clinical challenges. Current therapeutic strategies focus on rational combinations of targeted therapy, checkpoint blockade, IL-2-based approaches, oncolytic viruses, and adoptive cell therapies such as tumor-infiltrating lymphocytes to enhance response depth and durability. However, these intensified regimens carry increased toxicity risks, highlighting the need for improved patient selection and monitoring. Overall, emerging evidence supports a paradigm shift toward optimized treatment sequencing, response-adapted surgical strategies, and biomarker-guided personalization to maximize clinical benefit while minimizing toxicity.
MEMBER ACCOUNT
登录成功会直接打开下一页。