Cancer is the second leading cause of death globally one in six deaths, in 2018. As of 2020, there were 19.3 million people suffering from this condition, and it is predicted by World Health Organization that thisnumber will raise to 30.2 million in 20 years.
Despite the high burden of this disease and the increased efforts in the quest for a cure, the development of efficient universal therapies has not been achieved. The astonishing diversity of cancer types and different treatment responses of individuals carrying the same type of tumour presents a huge challenge that science and modern medicine have not yet been able to tackle. As such, common practice is still to resort to traditional practices such as chemotherapy, radiotherapy or surgery, known to increase the survival of several patients. However, not only there are severe systemic side effects associated with the non-specificity of these approaches but also many patients do no respond to treatment at all. This has powered cancer research in searching for novel therapies that would act by inducing a potent activation of the host immune system against tumour cells, leading to specific clearing this disease.
Immunotherapies for tumour treatment can be based in several technologies, such as targeted antibodies, immunomodulators, adoptive cell therapy and cancer vaccines, among others. Nanovaccines have the potential to tackle the lack of specificity of traditional therapies, by supporting an efficient delivery of antigens and adjuvants to target tissues. We believe that the success of cancer nanovaccines relies on promoting potency and durability of anti-tumour immunity. Accordingly, it is crucial that cancer nanovaccines efficiently set off the patient’s immune system. Thus, this projects focuses on the effects of nanovaccines on dendritic cells (DCs), which are first responders of the immune system and at the same time have the great ability of orchestrating a potent anti-tumour response. DCs are exceptionally specialized in capturing, processing and presenting antigens on MHCI I or II, thereby activating CD8+ or CD4+T cell responses, respectively. Potent activation of CD8+ T cells by DCs is pivotal during anti-tumour immunity, as CD8+ T cells induce tumour cell death. Moreover, DCs are essential players in polarising CD4+T cells, which primarily contribute to anti-tumour immune responses by aiding CD8+ T cells but are also important for long term anti-tumour immune memory. Hence, anti-tumour immunotherapy is only effective if we achieve successful boost of both responses by overcoming the immunosuppressive microenvironment allowing for an efficient DC-T cell crosstalk and subsequent potent anti-tumour T cell responses.
As new immunotherapy developments are increasingly combined with nanomedicines, understanding the interaction between DCs and nanoparticles is crucial for early stages in the development of safe and effective nano-based tumour vaccines. Therefore, we hypothesize that specific nanovaccine formulations – formulated by other partners within the DIRNANO consortium – have the potential to efficiently reactivate DCs following tolerogenization induced by the TME, driving strong and effective host anti-tumour immune responses.
Ana Rita Salgado Ribeiro - Early Stage Researcher
Department of Biosciences, Cancer Cluster Salzburg - Paris-Lodron University of Salzburg (Austria)