Abscopal Effect of Intratumoral Photodynamic Therapy Is Associated with Increased Tumor Directed T Cells

Introduction: Photodynamic therapy (PDT) consists of a light and drug combination delivered to a target organ. The photodynamic reaction caused by the generation of reactive oxygen species produces cell damage to the cell wall, endoplasmic reticulum, mitochondria and nucleus resulting in immunogenic cell death. We present a case of the abscopal effect of PDT in a pancreatic carcinoma patient then investigated the effects of PDT in on the peripheral blood mononuclear cells (PBMC) profile. Case Description/Methods: A 75-year-old White male with biopsy-proven Stage III (cT4, cNX, cM0) pancreatic uncinate process adenocarcinoma (5.6X2.3 cm) was referred to our institution. A chest CT scan showed multiple solid non-calcified pulmonary nodules measuring up to 1 X 0.7 cm. He was declared as a poor surgical candidate and was started on EUS-guided verteporfin-based PDT. Verteporfin was given intravenously 4 hours prior to photoradiation in a dose of 0.4 mg/kg of bodyweight. Then a 1 cm cylindrical diffusing fiber was placed via EUS into the tumor and photo-adiation performed at 150 milliwatts for 50 Joules. We found that the largest component of the mesenteric mass decreased by 1 cm and local pancreatic uncinated mass as well as distal pulmonary metastatic lesions decreased after 7 months of the first round of PDT. The right lower lobe pulmonary nodule and clustered micro-nodules in the left lower lobe have been resolved without additional chemotherapy. To examine the abscopal effect, we took peripheral blood samples from an 81-year-old WM with stage III (cT4, cN0, cM0) pancreatic cancer patient before and after intratumoral PDT. The blood was assessed by flow cytometry to examine the T cells population. We used red cell lysed whole blood, lymphocytes were determined by forward and side scatter profile. We determined the CD8 positive T cell population, tumor-reactive T cells(CD11a high PD-1+) and also the PD-1 therapy responsive( CX3CR1+ Granzyme B+ PD1+ ) T cells. We found that PD-1 therapy responsive T cells (CX3CR1+ Granzyme B+) had increased from 1.13 to 6.34% (p< 0.00001). Discussion: PDT is thought to be a localized tumor therapy but can produce tumor immunogenicity and abscopal effects in animal models. The treatment leads to significantly higher levels of tumor-directed T-cells that are responsive to anti-PD1 directed therapy. These observations suggest the potential of using PDT in combination with immune checkpoint inhibitors in pancreatic cancer.