Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 04 1 13 Fatemeh Eskandari-Malayeri Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Sajjad Shekarchian Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Esmaeil Mortaz Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Respiratory Immunology Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2025 06 26 2025 10 11 Non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) figure prominently in the list of prevalent and resistant cancers that reveal significant differences in response to immunotherapy. Neoantigens, specific antigens resulting from tumor mutations, play an important role in provoking immune responses and the success of immunotherapy. This review scrutinizes the quantitative and qualitative differences in neoantigens in NSCLC and PDAC and their impact on the efficacy of immunotherapy. The evidence suggests that the higher mutational burden, greater diversity, and different quality of neoantigens in NSCLC compared with PDAC are among the key drivers contributing to the enhanced susceptibility to immunotherapy in this cancer. These differences could pave the way for the development of personalized therapies and novel strategies to improve treatment outcomes in resistant cancers. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4499 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4499/2292