Abstract Inflammatory cells, most especially neutrophils, can be a necessary component of the antitumor activity occurring after administration photodynamic therapy. Generation neutrophil responses has been suggested to particularly important in instances when delivered therapy (PDT) dose is insufficient. In these cases, release granules and engagement immunity may play an role eliminating residual disease. Herein, we utilize vivo imaging luminol chemiluminescence noninvasively monitor...

Surgical cytoreduction for patients with malignant pleural mesothelioma (MPM) is used selected as a part of multi-modality management strategy. Our group has previously described the clinical use photodynamic therapy (PDT), form non-ionizing radiation, an intraoperative option MPM. Although necessary removal bulk disease, effects surgery on residual MPM burden are not understood. In this bedside-to-bench study, Photofrin-based PDT introduced possibility achieving long-term response in murine...

<p>Supplemental Figure 5. Gating Scheme for Splenocyte Immunophenotyping</p>

<p>CD8<sup>+</sup> T cells mediate a robust anti-PDT response and transfer antitumor activity. <b>A,</b> In mice bearing AB12 tumors, administration of CD8<sup>+</sup>-depleting antibodies prior to PDT (<i>n</i> = 13) impeded tumor compared with treated isotype control 12; <i>P</i> < 0.001). The median time growth the 400 mm<sup>3</sup> endpoint was 4–5 days in 9) or 3) absence PDT. <b>B,</b> were...

<p>TI does not significantly impede direct PDT damage. Clonogenic analysis of tumor tissue immediately (<b>A</b>) or 24 hours (<b>B</b>) after PDT. At TI and/or PDT, reductions were observed in the median number clonogenic cells per gram compared with untreated controls (9.3-fold change for TI, 5.9-fold and 4.9-fold TI/PDT). Significance was only TI/PDT group versus control (TC, <i>P</i> = 0.0192). <b>C,</b> Immunoblot PARP cleavage...

<div><p>Surgical cytoreduction for patients with malignant pleural mesothelioma (MPM) is used selected as a part of multi-modality management strategy. Our group has previously described the clinical use photodynamic therapy (PDT), form non-ionizing radiation, an intraoperative option MPM. Although necessary removal bulk disease, effects surgery on residual MPM burden are not understood. In this bedside-to-bench study, Photofrin-based PDT introduced possibility achieving...

<p>Immunophenotyping reveals increased granulocytes when TI precedes PDT. Flow cytometric analysis of splenocytes revealed no significant increase in CD8<sup><sup>+</sup></sup> or CD4<sup>+</sup> T cells at 2 days after administration TI, PDT, TI/PDT. Similarly, variations were observed CD4<sup>+</sup>FOXP3<sup>+</sup> Tregs. Mean fold change CD11b<sup>+</sup>Ly6G<sup>+</sup> TI/PDT significantly...

<p>Supplemental Figure 5. Gating Scheme for Splenocyte Immunophenotyping</p>

<p>TI does not significantly impede direct PDT damage. Clonogenic analysis of tumor tissue immediately (<b>A</b>) or 24 hours (<b>B</b>) after PDT. At TI and/or PDT, reductions were observed in the median number clonogenic cells per gram compared with untreated controls (9.3-fold change for TI, 5.9-fold and 4.9-fold TI/PDT). Significance was only TI/PDT group versus control (TC, <i>P</i> = 0.0192). <b>C,</b> Immunoblot PARP cleavage...

<div><p>Surgical cytoreduction for patients with malignant pleural mesothelioma (MPM) is used selected as a part of multi-modality management strategy. Our group has previously described the clinical use photodynamic therapy (PDT), form non-ionizing radiation, an intraoperative option MPM. Although necessary removal bulk disease, effects surgery on residual MPM burden are not understood. In this bedside-to-bench study, Photofrin-based PDT introduced possibility achieving...

<p>Optical properties, Photofrin content, and oxygenation are similar at the time of illumination in PDT- TI/PDT-treated tumors. <b>A,</b> Tumor optical properties were measured prior to immediately after TI exposure. After TI, tumors showed no difference mean average absorption (μ<sub>a</sub>, <i>P</i> = 0.690), effective coefficient (μ<sub>eff</sub>, 0.826), or reduced scattering (μ<sub>s</sub>’, 0.283). <i>n</i>...

<p>Supplemental Figure 4. PDT response is not altered when it followed by TI</p>

<p>Splenocyte cells from TI/PDT treated mice transfer immunosuppression that limits PDT-induced antitumor immunity. Splenocytes isolated the spleen of naïve mice, tumored or with TI, PDT, were transferred alongside AB12 into recipient mice. Daily average tumor volume in (<b>A</b>) and number days for growth to 150 mm<sup>3</sup> (<b>B</b>) are shown. whose tumors PDT significantly delayed tumors. Compared splenocytes receiving alone, received TI...

<p>Supplemental Figure 1. Growth Curves of Individual Mice Treated With Surgical Resection, Photodynamic Therapy, or Tumor Incisions</p>

<p>Supplemental Figure 3. Preceding PDT with TI significantly reduces response in male AB12-bearing mice</p>

<p>Supplemental Figure 1. Growth Curves of Individual Mice Treated With Surgical Resection, Photodynamic Therapy, or Tumor Incisions</p>

<p>Surgical resection, although necessary, limits the achievable PDT response of residual disease. Murine mesothelioma AB12 cells were implanted in flanks female syngeneic mice. <b>A,</b> Mice with 200 mm<sup>3</sup> tumors that surgically debulked by 60% (to ∼80 mm<sup>3</sup>) prior to (<i>n</i> = 10) achieved CRs (no regrowth after 90 days) and showed longer times than mice whose treated alone 5; <i>P</i> 0.115) or 0.008)....

<p>Optical properties, Photofrin content, and oxygenation are similar at the time of illumination in PDT- TI/PDT-treated tumors. <b>A,</b> Tumor optical properties were measured prior to immediately after TI exposure. After TI, tumors showed no difference mean average absorption (μ<sub>a</sub>, <i>P</i> = 0.690), effective coefficient (μ<sub>eff</sub>, 0.826), or reduced scattering (μ<sub>s</sub>’, 0.283). <i>n</i>...

<p>CD8<sup>+</sup> T cells mediate a robust anti-PDT response and transfer antitumor activity. <b>A,</b> In mice bearing AB12 tumors, administration of CD8<sup>+</sup>-depleting antibodies prior to PDT (<i>n</i> = 13) impeded tumor compared with treated isotype control 12; <i>P</i> < 0.001). The median time growth the 400 mm<sup>3</sup> endpoint was 4–5 days in 9) or 3) absence PDT. <b>B,</b> were...

<p>T cells and splenocyte from TI/PDT treated mice limit PDT-induced antitumor immunity in a C57BL/6 model of mesothelioma. Murine mesothelioma AE17o were implanted into the flank grown to 80 mm<sup>3</sup> prior treating with TI and/or PDT. <b>A,</b> Tumor responses PDT (<i>n</i> = 14) impeded by exposure 15; <i>P</i> 0.019 for vs. TI/PDT). Transferability tumors was assessed using CD8<sup>+</sup> T isolated splenocytes...

<p>Surgical resection, although necessary, limits the achievable PDT response of residual disease. Murine mesothelioma AB12 cells were implanted in flanks female syngeneic mice. <b>A,</b> Mice with 200 mm<sup>3</sup> tumors that surgically debulked by 60% (to ∼80 mm<sup>3</sup>) prior to (<i>n</i> = 10) achieved CRs (no regrowth after 90 days) and showed longer times than mice whose treated alone 5; <i>P</i> 0.115) or 0.008)....

<p>Immunophenotyping reveals increased granulocytes when TI precedes PDT. Flow cytometric analysis of splenocytes revealed no significant increase in CD8<sup><sup>+</sup></sup> or CD4<sup>+</sup> T cells at 2 days after administration TI, PDT, TI/PDT. Similarly, variations were observed CD4<sup>+</sup>FOXP3<sup>+</sup> Tregs. Mean fold change CD11b<sup>+</sup>Ly6G<sup>+</sup> TI/PDT significantly...

<p>Supplemental Figure 4. PDT response is not altered when it followed by TI</p>

<p>Supplemental Figure 2. TI promotes acute inflammation</p>

<p>Splenocyte cells from TI/PDT treated mice transfer immunosuppression that limits PDT-induced antitumor immunity. Splenocytes isolated the spleen of naïve mice, tumored or with TI, PDT, were transferred alongside AB12 into recipient mice. Daily average tumor volume in (<b>A</b>) and number days for growth to 150 mm<sup>3</sup> (<b>B</b>) are shown. whose tumors PDT significantly delayed tumors. Compared splenocytes receiving alone, received TI...