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 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.
Calzascia
Thomas
T
Laboratory of Tumour Immunology, Division of Oncology, Department of Neurosurgery, University Hospital Geneva, Rue Micheli-du-Crest 24, 1211 Geneva 14, Switzerland.
Di Berardino-Besson
Wilma
W
Wilmotte
Rick
R
Masson
Frédérick
F
de Tribolet
Nicolas
N
Dietrich
Pierre-Yves
PY
Walker
Paul R
PR
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D005260:Female; D005910:Glioma / Q000276:immunology* / Q000473:pathology; D007117:Immunization, Secondary; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte