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The Journal of Immunology, 2003, 171: 2187-2191.
Copyright © 2003 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: Cross-Presentation as a Mechanism for Efficient Recruitment of Tumor-Specific CTL to the Brain 1

Thomas Calzascia*, Wilma Di Berardino-Besson*, Rick Wilmotte*,{dagger}, Frédérick Masson*, Nicolas de Tribolet{dagger}, Pierre-Yves Dietrich* and Paul R. Walker2,*

* Laboratory of Tumour Immunology, Division of Oncology and {dagger} Department of Neurosurgery, University Hospital Geneva, Geneva, Switzerland

The number and localization of effector cells to the tumor site are crucial elements for immune rejection of solid tumors. However, for cerebral malignancies, antitumor responses need to be finely tuned to avoid neuropathologic consequences. In this study, we determine factors that regulate CTL localization and tumoricidal function after intracerebral implantation of tumors expressing model Ag. H-2bxd mice implanted with a CW3+ murine glioma lacking H-2Kd molecules necessary to present the CW3170–179 epitope demonstrate cross-priming of H-2Kd-restricted CTL, and moreover, Ag-dependent accumulation of functional H-2Kd/CW3170–179-specific CTL within the tumor bed. This implicates a role for cross-presentation not only in priming, but also in retention of fully differentiated CTL in the tumor stroma at the effector stage of the response. Modulating cross-presentation of Ag may be the key in regulating specific immune responses in the brain: either by augmenting protective responses or by down-modulating destructive autoimmune reactions.




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