Role of the immune system in mediating the antitumor effect of benzophenothiazine photodynamic therapy

The role of the host immune system in contributing to tumor regression foll owing benzophenothiazine photodynamic therapy (PDT) was examined. Photodyna mic therapy with 2-iodo-5-ethylamino-9-diethylaminobenzo[a]-phenothiazinium chloride (2I-EtNBS) eradicated EMT-6 mammary fibrosarcomas in 75-100% of t reated mice. In contrast, PDT failed to inhibit tumor growth in T-cell-defi cient nude mice. Furthermore, T-cell depletion studies with anti-CDS antibo dy revealed that the CD8(+) T-cell population was critical for an effective PDT response (tumor volume 14 days post-PDT: 262 mm(3) vs 59 mm3 in contro ls; P < 0.01), Because anti-CD4 antibody inhibited tumor growth in the abse nce of PDT, the role of CD4(+) T cells remains unclear. Depletion of natura l killer (NK) cells in vivo with anti-asialo-GM1 antibody significantly red uced a suboptimal PDT effect relative to vehicle controls (tumor volume 13 days post-PDT: 513 mm(3) vs 85 mm(3), respectively; P < 0.001). However, sp lenic NK cells obtained from PDT-treated tumor-bearing mice were not cytoto xic in vitro against EMT-6 cells, suggesting that NK cells contribute to th e PDT effect in vivo by an indirect mechanism. In addition, when mice with complete tumor regression following PDT were rechallenged 28 days later wit h 5 x 10(5) EMT-6 cells, tumor growth was signficantly inhibited as compare d to controls (tumor volume 40 days postrechallenge: 137 mm(3) vs 833 mm(3) 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 cell s contribute to this response and such PDT can elicit protective antitumor immunity.