Researchers are gaining new insights into why pancreatic ductal adenocarcinoma (PDAC), one of the deadliest forms of cancer, remains highly resistant to immunotherapy. A recent review highlights the complex roles of tumor-infiltrating B cells (TIBs) and tertiary lymphoid structures (TLSs), which can either support or suppress the body’s immune response against cancer.
The analysis found that some B-cell populations, such as regulatory B cells, help tumors evade immune attack by suppressing cancer-fighting T cells and natural killer cells. In contrast, plasma cells, naïve B cells, and memory B cells appear to strengthen anti-tumor immunity and are associated with longer patient survival.
TLSs, organized clusters of immune cells that form within tumors, also play an important role. Patients with mature TLSs located inside tumors tend to have significantly better outcomes, with survival extending well beyond that seen in patients with immature TLSs.
The review also helps explain why previous efforts to target harmful B cells, including trials of BTK inhibitors, have failed. Researchers suggest that broad B-cell depletion may unintentionally eliminate beneficial immune cells and TLSs.