Cross-priming of T cells to intracranial tumor antigens elicits an immune response that fails in the effector phase but can be augmented with local immunotherapy

Journal of Neuroimmunology
Simona VelicuMaciej S Lesniak

Abstract

Central nervous system (CNS) tumors are thought to be poorly immunogenic. However, whether defective anti-tumor immunity is a consequence of a relative failure of T cell priming versus a deficient effector phase of the anti-tumor immune response is not clear. We utilized a well-defined model system of B16 melanoma expressing the model antigen SIY-GFP to evaluate tumor antigen cross-priming and tumor rejection from the CNS versus subcutaneous compartments. We observed that B16-SIY cells implanted in the CNS were capable of inducing T cell priming as measured by IFN-gamma ELISPOT in the spleen. Cross-priming occurred in the absence of detectable systemic dissemination of the tumor. Despite the induction of a T cell response, CNS tumors grew progressively and were fatal, whereas the same tumor implanted in the flank was rejected. To study the effector phase of the immune response in more detail, in vitro primed 2C/RAG2-/- TCR transgenic CD8+ cells, which recognize the SIY peptide, were adoptively transferred. In addition, the CNS microenvironment was modulated by intracranial delivery of IL-2. While mice that received primed 2C cells alone showed an increase in survival, co-administration of intracranial IL-2 led to a marked prolo...Continue Reading

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Citations

Sep 16, 2006·Immunological Reviews·Thomas F GajewskiHelena Harlin
Mar 28, 2008·Immunological Reviews·Duane A MitchellJohn H Sampson
Jul 14, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Diana L ThomasEdward J Roy
Apr 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ashraful HaqueChristian R Engwerda
Jul 10, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Frédérick MassonPaul R Walker
Feb 26, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·William TomaszewskiJohn H Sampson

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