Case Report: An exceptional response to a novel immunotherapy-based combination treatment for resected pancreatic ductal adenocarcinoma with recurrence to the abdominal wall.

Pancreatic ductal adenocarcinoma (PDAC) is a difficult-to-treat cancer with a 5-year survival rate of only 13%. Intense chemotherapies are needed to control the disease. Surgical resection, if possible, is the only curative approach. However, recurrence rates are high. The inclusion of immune checkpoint inhibitors in treatment hasn't shown benefit, most likely because of the cancer's highly immunosuppressive tumor microenvironment (TME). Leukemia Inhibitory Factor (LIF) is a cytokine that contributes to this profound immunosuppression, which is thought to be at least partly mediated by pro-tumoral (M2-like) tumor-associated macrophages (TAMs). Those macrophages harbor LIF receptors on their surface. The addition of the anti-LIF antibody MSC-1 to a combination of anti-programmed death-ligand 1 (anti-PD-L1) and chemotherapy has shown encouraging preclinical results, successfully reversing pro-tumoral TAMs into anti-tumoral (M1-like) macrophages. Here, we report a patient with recurrent PDAC in the abdominal wall and peritoneum, that immediately went into complete remission after receiving an investigational treatment with MSC-1 and anti-PD-L1 combined with standard-of-care chemotherapy. We discuss immunological mechanisms that may have contributed to the impressive treatment response.