Immuno-Oncological Study of PFKL Targeting and Discovery of an Anti-Aging Microbiome

Abstract

Cancer immunotherapy and anti-aging therapies are among the hottest areas of research in modern medicine. This study explores both fields by identifying novel targets for cancer immunotherapy and discovering novel microbiome strains that exhibit anti-aging effects. First, we investigated the potential of phosphofructokinase (PFKL, liver type) as a novel therapeutic target for cancer immunotherapy from an immunological perspective. Analyzing clinical data, we found that patients with lower PFKL expression had a higher survival rate. Using CRISPR-Cas9-based gene editing technology, we created PFKL knockdown (KD) cells and performed a series of in vitro and animal model experiments. The results showed that the PFKL KD cell line induced antitumor effects through increased activation of T cells and other myeloid cells. These results suggest that PFKL may be a promising therapeutic target to improve the efficacy of cancer immunotherapy. Second, we demonstrated that gut microbial strains Lactococcus lactis LL23, GEN3013, and Bifidobacterium adescentis KCTC3216 can induce anti-aging effects. We first screened strains expressing key enzymes involved in the anti-aging pathway through cell experiments, and then used the selected strains in both cell and animal experiments to demonstrate their anti-aging efficacy. Furthermore, FACS analysis confirmed the anti-aging effects from an immunological perspective. These results highlight the therapeutic potential of these strains as new targets for anti-aging treatment. This study presents the possibility of overcoming the limitations of cancer immunotherapy and anti- aging treatments through two innovative approaches: PFKL KD and the discovery of new anti-aging strains. The findings provide a foundation for developing new therapeutic strategies in both fields and emphasize the practical applications of immunological and microbiological research.