英文原题:Cold and hot tumors: immunological determinants, cancer-immunity cycle dysregulation, and nanotechnology-driven therapeutic approaches.
癌症仍然是全球主要的健康负担,也是全球第二大死亡原因。
癌症仍然是全球主要的健康负担,也是全球第二大死亡原因。近年来癌症免疫治疗的进展强调了肿瘤微环境(TME)在决定治疗结局中的关键作用,从而将肿瘤分为免疫学上的“热”和“冷”表型。冷肿瘤的特征是免疫原性低、免疫细胞浸润有限以及高度免疫抑制的微环境,导致预后不良和对免疫检查点抑制剂耐药。尽管已开发出多种免疫治疗策略,但在冷肿瘤中有效激活抗肿瘤免疫仍然是一个重大的临床挑战。当前的方法旨在通过癌症疫苗和过继性T细胞转移等启动策略来启动免疫应答,同时通过免疫检查点阻断来克服免疫抑制信号。其他策略包括清除髓源性抑制细胞和增强共刺激通路。然而,这些方法往往受到递送效率低、肿瘤穿透性差和全身毒性的限制。纳米技术已成为肿瘤微环境重编程的一种有前景的平台。纳米载体能够实现免疫调节剂的靶向递送,增强抗原呈递,并在克服致密基质和异常血管等生物屏障的同时改善免疫激活。通过将纳米技术与免疫治疗相结合,为将冷肿瘤转化为热肿瘤、免疫应答性表型,从而提高治疗效果和临床结局带来了新的机遇。
Cancer remains a major global health burden and the second leading cause of mortality worldwide. Recent advances in cancer immunotherapy have emphasized the critical role of the tumor microenvironment (TME) in determining therapeutic outcomes, leading to the classification of tumors into immunologically "hot" and "cold" phenotypes. Cold tumors are characterized by low immunogenicity, limited immune cell infiltration, and a highly immunosuppressive microenvironment, resulting in poor prognosis and resistance to immune checkpoint inhibitors. Despite the development of multiple immunotherapeutic strategies, effective activation of antitumor immunity in cold tumors remains a major clinical challenge. Current approaches aim to initiate immune responses through priming strategies such as cancer vaccines and adoptive T-cell transfer, while simultaneously overcoming immunosuppressive signaling via immune checkpoint blockade. Additional strategies include depletion of myeloid-derived suppressor cells and enhancement of co-stimulatory pathways. However, these approaches are often limited by inefficient delivery, poor tumor penetration, and systemic toxicity. Nanotechnology has emerged as a promising platform for tumor microenvironment reprogramming. Nanocarriers enable targeted delivery of immunomodulatory agents, enhance antigen presentation, and improve immune activation while overcoming biological barriers such as dense stroma and abnormal vasculature. By integrating nanotechnology with immunotherapy, new opportunities arise to convert cold tumors into hot, immune-responsive phenotypes, thereby improving therapeutic efficacy and clinical outcomes.
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