Different Subsets of Tumor-Infiltrating Lymphocytes Correlate with Macrophage Influx and Monosomy 3 in Uveal Melanoma

Experimental cancer immunology and therap

Effect of Hypoxic Stress on Migration and Characteristics of Monocytes in Uveal Melanoma

Ophthalmic researc

Effect of hypoxic stress on induction and plasticity of tumor-induced immune cells in uveal melanoma

Experimental cancer immunology and therap

Peptide Vaccination after T-Cell Transfer Causes Massive Clonal Expansion, Tumor Eradication, and Manageable Cytokine Storm

Adoptive T-cell transfer (ACT) is successfully applied as a cancer treatment that is based on the activation and effector functions of tumor-specific T cells. Here, we present results from a mouse model in which ACT is combined with a long peptide-based vaccine comprising gp100 T-cell epitopes. Transferred CD8(+) T cells expanded up to 1,000-fold after peptide vaccination, leading to a 3-fold increase in white blood cell count and a very high frequency in the generation of antigen-specific memory T cells, the generation of which tended to correlate with effective antitumor responses. An enormous pool of effector T cells spread widely to different tissues, including the skin and the immune-privileged eye, where they mediate tumor eradication. Importantly, these striking T-cell dynamics occurred in immunocompetent mice without prior hematologic conditioning. Continued activation of the specific T-cell pool by vaccination led to strong T-cell-mediated cytokine storm and lethality due to multi-organ failure. However, this immunopathology could be prevented by controlling the rapid biodistribution of the peptide or by using a weakly agonistic peptide. Together, these results identify a peptide vaccination strategy that can potently accentuate effective ACT in non-lymphodepleted hosts. Cancer Res; 70(21); 8339-46. (C) 2010 AACR.Experimental cancer immunology and therap

Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma

Hereditary cancer genetic

Loss of BAPI expression is associated with increased angiogenesis in uveal melanoma

Experimental cancer immunology and therap