Photodynamic therapy-mediated immune response against subcutaneous mouse tumors.
The curative ability of photodynamic therapy (PDT) is severely compromised if treated tumors are growing in immunodeficient hosts. Reconstitution of severe combined immunodeficient (scid) mice with splenocytes from naive immunologically intact BALB/c mice did not improve the response to Photofrin-based PDT of EMT6 tumors growing in these animals. In contrast, adoptive transfer of BALB/c splenocytes containing EMT6 tumor-sensitized immune cells had a dramatic effect on tumor regrowth after PDT. For instance, full restoration of the curative effect of PDT was achieved with scid mice that received splenocytes from BALB/c donors that were cured of EMT6 tumors by PDT 5 weeks before adoptive transfer. Splenocytes obtained from donors cured of EMT6 tumors using X-rays were much less effective. Selective in vitro depletion of specific T-cell populations from engrafting splenocytes indicated that CTLs are the main immune effector cells responsible for conferring the curative outcome to PDT in this experimental model, whereas helper T lymphocytes play a supportive role. The immune specificity of these T-cell populations was demonstrated by the absence of cross-reactivity between the EMT6 and Meth-A tumor models (mismatch between tumors growing in splenocyte donors and recipients). The immunocompetent BALB/c mice that received adoptively transferred splenocytes containing PDT-generated, tumor-sensitized immune cells also benefited from the improved outcome of PDT of tumors they were bearing. This was demonstrated not only with the fairly immunogenic EMT6 tumor model but also with weakly immunogenic Line 1 carcinomas. The results of this study indicate that PDT is a highly effective means of generating tumor-sensitized immune cells that can be recovered from lymphoid sites distant to the treated tumor at protracted time intervals after PDT, which asserts their immune memory character. It is also shown that the treatment of tumors by PDT creates the conditions necessary for converting the inactive adoptively transferred pre-effector, tumor-sensitized immune cells into fully functional antitumor effector cells. An additional finding of this study is the evidence of NK cell activation in PDT-treated Meth-A sarcomas.
Korbelik
M
M
Cancer Imaging Department, British Columbia Cancer Agency, Vancouver, Canada. mkorbeli@bccancer.bc.ca
Dougherty
G J
GJ
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010778:Photochemotherapy; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured