Immunotherapy is emerging as a groundbreaking cancer treatment, offering the unprecedented opportunity to effectively treat and in several cases, even cure previously untreatable malignancies. Anti-tumour immunotherapies designed to amplify T cell responses against defined tumour antigens have long been considered effective approaches for cancer treatment. Despite a clear rationale behind such immunotherapies, extensive past efforts were unsuccessful in mediating clinically relevant anti-tumour activity in humans. This is mainly because tumours adopt specific mechanisms to circumvent the host´s immunity. Emerging data suggest that the full potential of cancer immunotherapy will be only achieved by combining immunotherapies designed to generate or amplify anti-tumour T cell responses with strategies able to impair key tumour immune-evasion mechanisms. However, many approaches aimed to re-shape the tumour immune microenvironment (TIME) are commonly associated with severe systemic toxicity, require frequent administration, and only show modest efficacy in clinical settings. The use of nanodelivery systems is revealing as a valid means to overcome these limitations by improving the targeting efficiency, minimising systemic exposure of immunomodulatory agents, and enabling the development of novel combinatorial immunotherapies. In this review, we examine the emerging field of therapeutic modulation of TIME by the use of nanoparticle-based immunomodulators and potential future directions for TIME-targeting nanotherapies.

中文翻译：

---

纳米免疫疗法：克服肿瘤免疫逃避。

免疫疗法正在成为一种开创性的癌症治疗方法，为有效治疗甚至治愈以前无法治愈的恶性肿瘤提供了前所未有的机会。长期以来，旨在放大针对特定肿瘤抗原的 T 细胞反应的抗肿瘤免疫疗法一直被认为是癌症治疗的有效方法。尽管这种免疫疗法背后有明确的理由，但过去的广泛努力在调节人类临床相关的抗肿瘤活性方面没有成功。这主要是因为肿瘤采用特定的机制来规避宿主的免疫。新兴数据表明，只有将旨在产生或放大抗肿瘤 T 细胞反应的免疫疗法与能够削弱关键肿瘤免疫逃避机制的策略相结合，才能充分发挥癌症免疫疗法的潜力。然而，许多旨在重塑肿瘤免疫微环境 (TIME) 的方法通常与严重的全身毒性相关，需要频繁给药，并且仅在临床环境中显示出适度的疗效。通过提高靶向效率、最大限度地减少免疫调节剂的全身暴露以及开发新型组合免疫疗法，纳米递送系统的使用被揭示为克服这些限制的有效手段。在本次审查中，