Abstract
BackgroundVaccination generating a robust memory population of CD8+ T cells may provide protection against cancer. However, immune therapies for cancer are influenced by the local tumour immune microenvironment. An infiltrate of T cells into tumours of people with colorectal cancer has proven to be a significant indicator of good prognosis.MethodsWe used an intracaecal mouse model of cancer to determine whether a protective immune response against a mucosal gut tumour could be generated using a systemic intervention. We investigated the generation of murine memory CD8+ T cells using a sustained antigen release vaccine vehicle (chitosan gel; Gel + OVA) containing the model antigen ovalbumin, chitosan gel alone (Gel) or conventional dendritic cell vaccination (DC + OVA) using the same protein antigen.ResultsFollowing vaccination with Gel + OVA, CD8+ T cell memory populations specific for ovalbumin protein were detected. Only vaccination with Gel + OVA gave decreased tumour burden compared to unvaccinated or DC + OVA-vaccinated mice in the intracaecal cancer challenge model.ConclusionThese results indicate that subcutaneous vaccination with Gel + OVA generates a population of functional CD8+ memory T cells in lymphoid tissue able to protect against intracaecal tumour challenge. Vaccination with chitosan gel may be valuable in anti-cancer treatment at both peripheral and mucosal sites.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0178-4) contains supplementary material, which is available to authorized users.
Highlights
Vaccination generating a robust memory population of CD8+ T cells may provide protection against cancer
We showed that vaccination with chitosan gel was protective in an intracaecal mouse model of cancer, while vaccination with DCs was not
Chitosan gel vaccine is protective in a mouse model of colorectal cancer We have previously demonstrated that subcutaneous injection with vaccine in a sustained release gel generated a population of CD8+ memory T cells at both peripheral lymphoid sites and gut-associated lymphoid sites [15]
Summary
Vaccination generating a robust memory population of CD8+ T cells may provide protection against cancer. An infiltrate of T cells into tumours of people with colorectal cancer has proven to be a significant indicator of good prognosis. The immune system plays a large role in the control of disease. The gut is an immunosuppressive environment and control of local disease may be altered. In many cancers an increased frequency of infiltrating regulatory T cells (Tregs) correlates with poor outcome but in colorectal cancer, the infiltrate of Tregs has been associated with both good and poor outcomes [7]. Orthotopic models of colorectal cancer have been described [9,10,11,12,13,14], but we wished to investigate the ability to modulate the systemic immune response to prevent local tumour growth in the gut
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