Treatment of malignant pleural mesothelioma remains palliative in nature, and consists of surgical resection in order to achieve local control. More recently, surgical procedures which spare the lung (radical pleurectomy) have been coupled with photodynamic therapy (PDT) of residual disease to achieve better local control. Due to increasing evidence of the effects of surgery on both host immunity and residual tumor cells, we investigated the contribution of injuries sustained during surgery to efficacy of photodynamic therapy in a mouse model of malignant mesothelioma. We previously observed that surgical injury prior to PDT inhibits long-term response in vivo. As it relates to PDT outcome, we are now investigating neutrophil profiles in the presence and absence of surgical injury. Our results demonstrate that neutrophil influx into the tumor and lymph node occur sooner when PDT is preceded by surgical injury, as demonstrated by higher neutrophil counts in the respective tissue. Through in vivo imaging using luminol chemiluminescence as a marker of neutrophil activation, we show a role of neutrophil-secreted myeloperoxidase activity in producing long-term response after PDT. However, myeloperoxidase deposition in the lymph node is known to suppress dendritic cell migration, activation, and antigen uptake. Thus, we are currently investigating if early influx and activation of neutrophils in tumor draining lymph nodes results in a loss of establishment of PDT-mediated immunity. Taken together, these studies will describe potential immunomodulatory roles for myeloperoxidase in responses to intraoperative PDT.
Richard W. Davis, Emma Snyder, Joann Miller, Astero Klampatsa, Steven Maceyko, Steven Albelda, Keith Cengel, and Theresa M. Busch, "Myeloperoxidase as an immunomodulator in intraoperative photodynamic therapy (Conference Presentation)," Proc. SPIE 10476, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVII, 104760G (Presented at SPIE BiOS: January 28, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2297115.5751479140001.
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