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.
