RESUMO
In view of the severe downsides of conventional cancer therapies, the quest of developing alternative strategies still remains of critical importance. In this regard, antigen cross-presentation, usually employed by dendritic cells (DCs), has been recognized as a potential solution to overcome the present impasse in anti-cancer therapeutic strategies. It has been established that an elevated cytotoxic T lymphocyte (CTL) response against cancer cells can be achieved by targeting receptors expressed on DCs with specific ligands. Glycans are known to serve as ligands for C-type lectin receptors (CLRs) expressed on DCs, and are also known to act as a tumor-associated antigen (TAA), and, thus, can be harnessed as a potential immunotherapeutic target. In this scenario, integrating the knowledge of cross-presentation and glycan-conjugated nanovaccines can help us to develop so called 'glyco-nanovaccines' (GNVs) for targeting DCs. Here, we briefly review and analyze the potential of GNVs as the next-generation anti-tumor immunotherapy. We have compared different antigen-presenting cells (APCs) for their ability to cross-present antigens and described the potential nanocarriers for tumor antigen cross-presentation. Further, we discuss the role of glycans in targeting of DCs, the immune response due to pathogens, and imitative approaches, along with parameters, strategies, and challenges involved in cross-presentation-based GNVs for cancer immunotherapy. It is known that the effectiveness of GNVs in eradicating tumors by inducing strong CTL response in the tumor microenvironment (TME) has been largely hindered by tumor glycosylation and the expression of different lectin receptors (such as galectins) by cancer cells. Tumor glycan signatures can be sensed by a variety of lectins expressed on immune cells and mediate the immune suppression which, in turn, facilitates immune evasion. Therefore, a sound understanding of the glycan language of cancer cells, and glycan-lectin interaction between the cancer cells and immune cells, would help in strategically designing the next-generation GNVs for anti-tumor immunotherapy.
RESUMO
Dendritic cells (DCs) present exogenous antigens on major histocompatibility complex (MHC) class I molecules, thereby activating CD8+ T cells, contributing to tumor elimination through a mechanism known as antigen cross-presentation. A variety of factors such as maturation state of DCs, co-stimulatory signals, T-cell microenvironment, antigen internalization routes and adjuvants regulate the process of DC-mediated antigen cross-presentation. Recently, the development of successful cancer immunotherapies may be attributed to the ability of DCs to cross-present tumor antigens. In this review article, we focus on the underlying mechanism of antigen cross-presentation and ways to improve antigen cross-presentation in different DC subsets. We have critically summarized the recent developments in the generation of novel nanovaccines for robust CD8+ T-cell response in cancer. In this context, we have reviewed nanocarriers that have been used for cancer immunotherapeutics based on antigen cross-presentation mechanism. Additionally, we have also expressed our views on the future applications of this mechanism in curing cancer.