Postoperative anti-PD-1 antibody treatment to reduce recurrence in a cancer ablation surgical wound

Abstract

BackgroundPostoperative radiation and chemotherapy are routinely applied for microscopic residual diseases; however, treatment outcomes are not optimal, and patients frequently suffer from treatment-related toxicities. To search for an effective and less-toxic adjuvant treatment for patients with high risk of recurrence, the preventive effect of anti-programmed cell death protein 1 (PD-1) treatment was evaluated in an in vivo animal model of post-surgical tumor recurrence. Materials and methodsAn animal model of postsurgical tumor recurrence (SCCVII tumors in C3H mice) was established by reinoculating tumor cells (105 cells) into surgical wound of primary tumor resection. Initial and recurrent tumors were compared by an immunohistochemistry and complementary DNA microarray. Using this in vivo model, tumor recurrence rates were evaluated in the animals receiving anti-PD-1 treatments. Animals were rechallenged with tumor cells, and interferon gamma secretion from spleen cells was analyzed to determine tumor-specific antitumor immunity. ResultsFoxP3high cell population was significantly elevated in recurrent tumors compared with that in primary tumors. Some immune response–related factors (granzyme F, neuronal leucine-rich repeat protein 1, myosin heavy chain 3, and transmembrane protein 8C) showed significant differences between primary and recurrent tumors. In this animal model, anti-PD-1 treatments significantly suppressed tumor recurrence. Importantly, tumor induction was significantly reduced when anti-PD-1–treated mice were rechallenged with tumor cells. Tumor cell–specific interferon gamma production was increased in these animals. ConclusionsPostoperative anti-PD-1 treatment significantly reduced recurrence in a cancer ablation surgical wound in an in vivo model of tumor recurrence. Our data lay the preclinical groundwork for the future clinical validation of adjuvant anti-PD-1 treatments in patients.