Pancreatic ductal adenocarcinoma (PDAC) is the seventh
most common
cause of cancer-related mortality. Despite different methods of treatment,
nearly more than 90% of patients with PDAC die shortly after diagnosis.
Contrary to promising results in other cancers, immune checkpoint
inhibitors (ICIs) showed limited success in PDAC. Recent studies have
shown that noncoding RNAs (ncRNAs) are extensively involved in PDAC
cell–immune cell interaction and mediate immune evasion in
this vicious cancer. PDAC cells recruit numerous ncRNAs to widely
affect the phenotype and function of immune cells through various
mechanisms. For instance, PDAC cells upregulate miR-301a and downregulate
miR-340 to induce M2 polarization of macrophages or overexpress miR-203,
miR-146a, and miR-212-3p to downregulate toll-like receptor 4 (TLR4),
CD80, CD86, CD1a, major histocompatibility complex (MHC) II, and CD83,
thereby evading recognition by dendritic cells. By downregulating
miR-4299 and miR-153, PDAC cells can decrease the expression of NK
group 2D (NKG2D) and MHC class I chain-related molecules A and B (MICA/B)
to blunt the natural killer (NK) cell response. PDAC cells also highly
express lncRNA AL137789.1, hsa_circ_0046523, lncRNA LINC00460, and
miR-155-5p to upregulate immune checkpoint proteins and escape T cell
cytotoxicity. On the other hand, ncRNAs derived from suppressive immune
cells promote proliferation, invasion, and drug resistance in PDAC
cells. ncRNAs can be applied to overcome resistance to ICIs, monitor
the immune microenvironment of PDAC, and predict response to ICIs.
This Review article comprehensively discusses recent findings regarding
the roles of ncRNAs in the immune evasion of PDAC.