Neoantigen-based immunotherapy in pancreatic ductal adenocarcinoma (PDAC)

摘要

Neoantigens generated in neoplasms are a type of protein completely absent in healthy tissues. Therefore, anti-tumor immunity targeting neoantigens is highly specific, which provides an optional approach to boost tumor immunotherapy. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies in humans, with few efficient treatments to improve its prognosis. Therefore, immunotherapies reinforced by neoantigen-based strategies should be considered. In PDAC, the mutational burden is intermediate compared with other common malignancies, while the naturally formed tumor immunity is significantly inferior. Moreover, the high mutation load in PDAC correlates with a poor clinical prognosis, although the combination of a large mutation repertoire and competent T cell population is indispensable for long-term survival. In clinical practice, three strategies have been mainly used: peptide or tumor cell vaccines, neo-epitope-coding nucleotide vaccines, and dendritic cell vaccines. However, three major problems remain to be addressed, including (1) highly personalized protocols after sampling, (2) insufficient neoantigen quantity, and (3) ineffective immunotherapy of PDAC. In summary, neoantigen-based therapy of PDAC is increasing and the treatment methods are accompanied by great challenges. Currently, extensive development is needed for effective neoantigen-based therapy.