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

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 loca...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2003-09, Vol.171 (5), p.2187-2191
Main Authors: Calzascia, Thomas, Di Berardino-Besson, Wilma, Wilmotte, Rick, Masson, Frederick, Tribolet, Nicolas de, Dietrich, Pierre-Yves, Walker, Paul R
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation - immunology
Antigen-Presenting Cells - immunology
Antigen-Presenting Cells - metabolism
Antigens, Viral - immunology
Antigens, Viral - metabolism
Brain Neoplasms - immunology
Brain Neoplasms - pathology
Cell Line, Tumor
Cytotoxicity, Immunologic
Epitopes, T-Lymphocyte - physiology
Female
Glioma - immunology
Glioma - pathology
Immunization, Secondary
Life Sciences
Lymphocyte Activation - immunology
Lymphocytes, Tumor-Infiltrating - immunology
Lymphocytes, Tumor-Infiltrating - pathology
Lymphocytic choriomeningitis virus - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred DBA
Neoplasm Transplantation
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - pathology
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Summary: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-2(bxd) mice implanted with a CW3(+) murine glioma lacking H-2K(d) molecules necessary to present the CW3(170-179) epitope demonstrate cross-priming of H-2K(d)-restricted CTL, and moreover, Ag-dependent accumulation of functional H-2K(d)/CW3(170-179)-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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.171.5.2187