Abstract
Cancer vaccines can induce robust activation of tumor-specific CD8 + T cells that can destroy tumors. Understanding the mechanism by which cancer vaccines work is essential in designing next-generation vaccines with more potent therapeutic activity. We recently reported that short peptides emulsified in poorly biodegradable, Incomplete Freund's Adjuvant (IFA) primed CD8+ T cells that did not localize to the tumor site but accumulated at the persisting, antigen-rich vaccination site. The vaccination site eventually became a T cell graveyard where T cells responded to chronically released gp100 peptide by releasing cytokines, including interferon-γ (IFN-γ), which in turn upregulated Fas ligand (FasL) on host cells, causing apoptosis of Fas+ T cells. T cells that escaped apoptosis rapidly became exhausted, memory formation was poor, and therapeutic impact was minimal. Replacing the non-biodegradable IFA-based formulation with water-based, short-lived formulation in the presence of immunostimulatory molecules allowed T cells to traffic to tumors, causing their regression. In this review, we discuss recent advances in immunotherapeutic approaches that could enhance vaccine-primed immune cells fitness and render the tumor microenvironment more accessible for immune cell infiltration.
Original language | English (US) |
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Pages (from-to) | 46-50 |
Number of pages | 5 |
Journal | International Journal of Biochemistry and Cell Biology |
Volume | 53 |
DOIs | |
State | Published - Aug 2014 |
Keywords
- Cancer
- Immunotherapy
- Inflammation
- T cells
- Trafficking
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
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