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Photodynamic Therapy Enhancement of Antitumor Immunity Is Regulated by Neutrophils

Department of Cell Stress Biology and the Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, New York

Requests for reprints: Sandra O. Gollnick, Photodynamic Therapy Center, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263. Phone: 716-845-8877; Fax: 716-845-8920; E-mail: sandra.gollnick{at}roswellpark.org.

Photodynamic therapy (PDT) is a Food and Drug Administration–approved local cancer treatment that can be curative of early disease and palliative in advanced disease. PDT of murine tumors results in regimen-dependent induction of an acute local inflammatory reaction, characterized in part by rapid neutrophil infiltration into the treated tumor bed. In this study, we show that a PDT regimen that induced a high level of neutrophilic infiltrate generated tumor-specific primary and memory CD8⁺ T-cell responses. In contrast, immune cells isolated from mice treated with a PDT regimen that induced little or no neutrophilic infiltrate exhibited minimal antitumor immunity. Mice defective in neutrophil homing to peripheral tissues (CXCR2^–/– mice) or mice depleted of neutrophils were unable to mount strong antitumor CD8⁺ T-cell responses following PDT. Neutrophils seemed to be directly affecting T-cell proliferation and/or survival rather than dendritic cell maturation or T-cell migration. These novel findings indicate that by augmenting T-cell proliferation and/or survival, tumor-infiltrating neutrophils play an essential role in establishment of antitumor immunity following PDT. Furthermore, our results may suggest a mechanism by which neutrophils might affect antitumor immunity following other inflammation-inducing cancer therapies. Our findings lay the foundation for the rational design of PDT regimens that lead to optimal enhancement of antitumor immunity in a clinical setting. Immune-enhancing PDT regimens may then be combined with treatments that result in optimal ablation of primary tumors, thus inhibiting growth of primary tumor and controlling disseminated disease. [Cancer Res 2007;67(21):10501–10]