Abstract
Myeloid regulatory cells (Mregs) are, together with regulatory T cells (Tregs), a dominant effector population responsible for restriction of the duration and strength of antitumor immune response. Photodynamic therapy (PDT) and cancer vaccines generated by PDT are modalities whose effectiveness in tumor destruction is closely dependent on the associated antitumor immune response. The present study investigated whether the immunodepletion of granulocytic Mregs in host mice by anti-GR1 antibody would improve the response of tumors to PDT or PDT vaccines in these animals. Anti-GR1 administration immediately after Temoporfin-PDT of mouse SCCVII tumors abrogated curative effect of PDT. The opposite effect, increasing PDT-mediated tumor cure-rates was attained by delaying anti-GR1 treatment to 1 h post PDT. With PDT vaccines, multiple anti-GR1 administrations (days 0, 4, and 8 post vaccination) improved the therapy response with SCCVII tumors. The results with PDT suggest that neutrophils (boosting antitumor effect of this therapy) that are engaged immediately after photodynamic light treatment are within one hour replaced with a different myeloid population, presumably Mregs that hampers the therapy-mediated antitumor effect. Anti-GR1 antibody, when used with optimal timing, can improve the efficacy of both PDT of tumors in situ and PDT-generated cancer vaccines.
Highlights
The field of cancer immunotherapy has made highly important progress during the past decade, by developing a number of potent antitumor immunity activation protocols [1]
We have recently shown that myeloid regulatory cells (Mregs), together with Tregs, have a critical negative impact on therapy outcome with photodynamic therapy (PDT)-generated cancer vaccines [8]
The results indicate that GR1 treatment can deplete mature neutrophils and tumor-sensitized granulocytic Mregs and can drastically alter therapy outcome after PDT or PDT vaccine application
Summary
The field of cancer immunotherapy has made highly important progress during the past decade, by developing a number of potent antitumor immunity activation protocols [1]. Cancers 2016, 8, 94 clinically established treatment for malignant and other diseases based on the use of visible light for activating photosensitizing drugs to produce cytotoxic reactive oxygen species [9], its exploitation for creating therapeutic cancer vaccines remains in pre-clinical stage of investigation [10]. We investigated the use of anti-mouse GR1antibody produced by hybridomas clone RB6-8C5 in elucidating the role of granulocytic myeloid populations in therapeutic outcome of tumor treatment by PDT and PDT vaccines. This antibody binds to mouse myeloid differentiation antigen and is known to effectively deplete granulocytes from mice [12]. The results indicate that GR1 treatment can deplete mature neutrophils and tumor-sensitized granulocytic Mregs and can drastically alter therapy outcome after PDT or PDT vaccine application
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