Research progress on the influence of tumor microenvironment on immunotherapy for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy associated with a poor prognosis and considerable resistance to conventional therapies. While radical surgery may offer benefit for a subset of patients with early-stage disease, recent decades have witnessed notable progress in immunotherapy, yielding encouraging outcomes across both hematologic cancers and solid tumors in preclinical and clinical settings. Despite these advances, PDAC remains largely refractory to current immunotherapeutic strategies, owing largely to its unique tumor microenvironment (TME). The TME plays a pivotal role in modulating tumor progression, metastatic dissemination, and treatment response. It is commonly marked by a profoundly immunosuppressive milieu that attenuates effective anti-tumor immunity and complicates therapeutic intervention. The complex cellular and molecular composition of the TME poses significant challenges for the development of novel treatment modalities. Consequently, there is a growing imperative to therapeutically "reprogram" various components and functions within the TME to improve clinical outcomes in PDAC patients. This review seeks to elucidate how the PDAC TME and its key immunosuppressive constituents influence disease progression and response to immunotherapy. A deeper understanding of these interactions may open avenues for innovative treatment approaches capable of overcoming the barriers imposed by the TME in pancreatic cancer.