Mreg Activity in Tumor Response to Photodynamic Therapy and Photodynamic Therapy-Generated Cancer Vaccines

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.

Luminol Chemiluminescence Reports Photodynamic Therapy‐Generated Neutrophil Activity In Vivo and Serves as a Biomarker of Therapeutic Efficacy

“…Contrastingly, neutrophil presence at the 4 h timepoint may be detrimental. In a previous study, Gr‐1 + cells found beyond the 1 h timepoint were associated with immunosuppressive functions . Referred to as Mregs by these researchers, the cell markers are comparable to that of the modern definition of myeloid‐derived suppressor cells.…”

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

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“…Kobayashi et al also reported success in Treg immunodepletion with only IR700 conjugated F(ab′) 2 fragments generated from an anti‐CD25 antibody . Working along similar cell immunodepletion mechanism, the use of anti‐GR1 antibody to target another population of immunosuppressing cells, namely, MDSCs cells provides another avenue to inhibit negative immunoregulatory effects that restricts the strength and duration of antitumor immune response …”