Abstract
Background: Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. Unfortunately, only 10–20% of PC patients are candidates for surgery, with the vast majority of patients with locally-advanced disease undergoing chemotherapy and/or radiation therapy (RT). Current treatments are clearly inadequate and novel strategies are crucially required. We investigated a novel tripartite treatment (combination of tumor targeted hyperthermia (HT), radiation therapy (RT), and immunotherapy (IT)) to alter immunosuppressive PC-tumor microenvironment (TME). (2). Methods: In a syngeneic PC murine tumor model, HT was delivered before tumor-targeted RT, by a small animal radiation research platform (SARRP) followed by intraperitoneal injections of cytotoxic T-cell agonist antibody against OX40 (also known as CD134 or Tumor necrosis factor receptor superfamily member 4; TNFRSF4) that can promote T-effector cell activation and inhibit T-regulatory (T-reg) function. (3). Results: Tripartite treatment demonstrated significant inhibition of tumor growth (p < 0.01) up to 45 days post-treatment with an increased survival rate compared to any monotherapy. Flow cytometric analysis showed a significant increase (p < 0.01) in cytotoxic CD8 and CD4+ T-cells in the TME of the tripartite treatment groups. There was no tripartite-treatment-related toxicity observed in mice. (4). Conclusions: Tripartite treatment could be a novel therapeutic option for PC patients.
Highlights
Pancreatic cancer (PC) is the fourth most lethal cancer in the United States
We have examined could be augmented by combining immunotherapy and hyperthermia [7,8,9,10,11,12] to treat locally-advanced whether radiation therapy (RT) could be augmented by combining immunotherapy and hyperthermia [7,8,9,10,11,12] to treat pancreatic cancer (LAPC)
Using a syngeneic mouse-tumor model with subcutaneously implanted panc02 cells, we tested the efficacy of tripartite treatment of combined hyperthermia (HT), radiation therapy (RT), and OX40 immunotherapy (IT)
Summary
Pancreatic cancer (PC) is the fourth most lethal cancer in the United States. In 2020, there will be an estimated diagnosis of 57,600 new cases, and 47,050 deaths [1]. Cancers 2020, 12, 1015 the approximately 40% of locally-advanced pancreatic cancer (LAPC) patients that are not qualified for resectable surgery are being continuously developed. The current treatment paradigms for pancreatic cancer involving surgery, chemotherapy, and/or radiation therapy (RT) have certainly shown survival improvements, but only for a margin of patients (i.e., resectable, margin-negative patients), Cancers. Novel therapeutic advances or improved treatment modalities are desperately needed. Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. Only 10–20% of PC patients are candidates for surgery, with the vast majority of patients with locally-advanced disease undergoing chemotherapy and/or radiation therapy (RT). We investigated a novel tripartite treatment (combination of tumor targeted hyperthermia (HT), radiation therapy (RT), and immunotherapy (IT)) to alter immunosuppressive. Conclusions: Tripartite treatment could be a novel therapeutic option for PC patients
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