title: Cancer vaccines: Trafficking of tumor-specific T cells to tumor after therapeutic vaccination.
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.
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yared
authors.initials: Y
authors.lastname: Hailemichael
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: WOverwijk@mdanderson.org.
authors.forename: Willem W
authors.initials: WW
authors.lastname: Overwijk
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D053222:Fas Ligand Protein / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*; D058951:gp100 Melanoma Antigen / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D053222:Fas Ligand Protein; D010446:Peptide Fragments; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma
keywords: Cancer; Immunotherapy; Inflammation; T cells; Trafficking