article · Molecular Biomedicine
Cancer immunotherapy outcomes depend significantly on the tumour microenvironment. Tumours are categorised as immunologically cold or hot. Cold tumours exhibit low immunogenicity, scarce immune cell infiltration, and strong immunosuppression, which leads to poor prognoses and resistance to immune checkpoint inhibitors. Existing techniques seek to trigger immunity via cancer vaccines, adoptive T-cell transfer, checkpoint inhibition, co-stimulatory pathway enhancement, and the depletion of myeloid-derived suppressor cells. Even so, these therapies face difficulties such as inefficient delivery, poor tumour penetration, and systemic toxicity. Nanotechnology offers solutions through nanocarriers that deliver immunomodulatory agents directly, improve antigen presentation, and bypass physical obstacles like dense stroma and abnormal blood vessels. Combining nanotechnology with immunotherapy provides a method to reprogramme the tumour microenvironment, transforming cold tumours into responsive hot tumours to enhance treatment success.
Many cancers fail to respond to standard immunotherapies because the surrounding tissue suppresses immune cells. Understanding how nanocarriers can overcome physical barriers and deliver immune-stimulating agents provides a pathway to make previously untreatable, cold tumours sensitive to immune attacks, ultimately expanding the reach and success rate of cancer treatments.
The described approaches point towards the development of nanotechnology-enabled drug delivery systems and combination immunotherapies for oncology drug developers and clinical oncologists. Because the focus centres on addressing delivery barriers, systemic toxicity, and microenvironment reprogramming, the underlying concepts represent early-stage development and preclinical or translational research, requiring substantial formulation optimisation and clinical validation before reaching market adoption.
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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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DOI: 10.1186/s43556-026-00534-0
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