Abstract
There is great interest in developing efficient therapeutic cancer vaccines, as this type of therapy allows targeted killing of tumor cells as well as long-lasting immune protection. High levels of tumor-infiltrating CD8+ T cells are associated with better prognosis in many cancers, and it is expected that new generation vaccines will induce effective production of these cells. Epigenetic mechanisms can promote changes in host immune responses, as well as mediate immune evasion by cancer cells. Here, we focus on epigenetic modifications involved in both vaccine-adjuvant-generated T cell immunity and cancer immune escape mechanisms. We propose that vaccine-adjuvant systems may be utilized to induce beneficial epigenetic modifications and discuss how epigenetic interventions could improve vaccine-based therapies. Additionally, we speculate on how, given the unique nature of individual epigenetic landscapes, epigenetic mapping of cancer progression and specific subsequent immune responses, could be harnessed to tailor therapeutic vaccines to each patient.
Highlights
To address the possibility of designing therapeutic cancer vaccines to work optimally in patients whose immune system may have been epigenetically modified, either by cancer cell-driven immunomodulation or by other external cues such as previous chemotherapy, it is first necessary to understand the different types of epigenetic imprinting that may be induced by vaccine therapy
In combination with tumor-specific-peptide-based vaccines, such as NY-ESO-1 and MART1, CpG oligodeoxynucleotide (CpG-ODN) resulted in elevated CD8+ T cell responses, tumor eradication was rarely achieved [115]
Several delivery systems, including virosomes, liposomes, virallike proteins (VLPs), and immune-stimulating complexes (ISCOMs) have been developed and used in clinical trials to improve the efficacy of cancer vaccines
Summary
Patients need to increase both the number and functionality of their cancer-specific T cells This currently can be achieved by de novo generation of T cellmediated immunity [15,16,17,18], through presentation by DCs [19, 20]. Understanding and modifying the epigenetic imprint of DC ex vivo [26], for example by the use of epigenetic modulators during tumor antigen loading, offers an intriguing avenue for future therapeutic exploration Another strategy that currently holds promise in cancer vaccine development includes the injection of antigenic peptides or genetic material encoding for these peptides, in combination with adjuvants, to target DCs in vivo. Despite appropriate antigen and adjuvant selections, many therapeutic cancer vaccines still fail to provide sustained T cell immunity, due to the many immune escape mechanisms available to neoplastic cells
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