Nano-immunotherapy: Overcoming tumour immune evasion.

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.