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Cell-mediated tumour immunity following photodynamic therapy with benzoporphyrin derivative monoacid ring A

University of British Columbia

Using the Winn tumour inhibition assay, lymphocytes from the lymph nodes but not the spleens of DBA/2 mice that had been cured of their Ml rhabdomyosarcoma with benzoporphyrin derivative monoacid ring A (BPD)-sensitized photodynamic therapy (PDT) were able to inhibit the growth of the Ml tumour in naive animals. Characterization of the lymph node cells through immuno-magnetic bead depletion showed that the tumour inhibitory activity was independent of B-cells and CD8+ cells. The CD4+-enriched lymph node cells were assessed for their T helper phenotype using intracellular cytokine staining and a polarization to T helper 1 or 2 was not observed during tumour growth or following PDT. However, intracellular cytokine staining did reveal that the activation state of the CD4+-enriched cells decreased during tumour growth and was partially restored following PDT. Ml tumour cells expressed high levels of stress proteins both in vitro and in vivo following treatment with BPD-sensitized PDT and the stress proteins were prepared from Ml cells for the analysis of in vitro proliferative responses of immune lymph node cells. Unseparated lymph node cells from PDT-treated animals responded in vitro to nitrocellulose preparations of 4 high molecular weight stress proteins and following optimization of the in vitro proliferation assay, a high degree of proliferation towards grp80 was detected. In contrast, CD4+- enriched cells from the lymph nodes of treated animals proliferated towards the Ml stress proteins in a manner that did not differ significantly from control lymph node cells. Following incubation of CD4+-enriched lymphocytes with nitrocellulose preparations of pure stress proteins prepared from two-dimensional gels, tumour inhibitory activity was maintained specifically in the presence of the hsp90 preparation that was at least as effective as freshly isolated CD4+ cells from PDT treated animals. For the first time, cell-mediated tumour immunity has been identified and characterized in the lymph nodes of animals treated with PDT. The antigenic target of the CD4+ cell tumour activity remains ambiguous as the response to stress proteins in vitro was not specific to PDT-treated animals; however, the presence of one of the stress proteins, hsp90, was able to maintain a high level of tumour inhibitory activity in vitro and may represent a signal of tissue damage that regulates cell-mediated tumour immunity. [Scientific formulae used in this abstract could not be reproduced.]

Thesis/Dissertation

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2009-05-29

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http://hdl.handle.net/2429/8476

Microbiology and Immunology

University of British Columbia

UBCV

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