The role of the host immune system in contributing to
tumor regression following
benzophenothiazine photodynamic therapy (
PDT) was examined.
Photodynamic therapy with 2-iodo-5-ethylamino-9-diethylaminobenzo[a]-phenothiazinium
chloride (2I-EtNBS) eradicated EMT-6 mammary
fibrosarcomas in 75-100% of treated mice. In contrast,
PDT failed to inhibit
tumor growth in T-cell-deficient nude mice. Furthermore, T-cell depletion studies with anti-CD8 antibody revealed that the CD8+ T-cell population was critical for an effective
PDT response (
tumor volume 14 days post-
PDT: 262 mm3 vs 59 mm3 in controls; P < 0.01). Because anti-CD4 antibody inhibited
tumor growth in the absence of
PDT, the role of CD4+ T cells remains unclear. Depletion of natural killer (NK) cells in vivo with anti-asialo-GM1 antibody significantly reduced a suboptimal
PDT effect relative to vehicle controls (
tumor volume 13 days post-
PDT: 513 mm3 vs 85 mm3, respectively; P < 0.001). However, splenic NK cells obtained from
PDT-treated
tumor-bearing mice were not cytotoxic in vitro against EMT-6 cells, suggesting that NK cells contribute to the
PDT effect in vivo by an indirect mechanism. In addition, when mice with complete
tumor regression following
PDT were rechallenged 28 days later with 5 x 10(5) EMT-6 cells,
tumor growth was significantly inhibited as compared to controls (
tumor volume 40 days postrechallenge: 137 mm3 vs 833 mm3 in controls; P < 0.03; percent animals without
tumor in five experiments: 67% vs 8% in controls). Collectively, these results demonstrate that CD8+ T cells are required to prevent
tumor regrowth after 2I-EtNBS-PDT, NK cells contribute to this response and such
PDT can elicit protective antitumor immunity.