Integrating a fasting mimicking diet to augment antitumor immunity following adoptive cell transfer in breast cancer

Cancer arises within a complex cellular milieu, where the extent and composition of tumor–infiltrating immune cells strongly influence tumor progression and patient prognosis. Emerging research highlights the therapeutic potential of fasting mimicking diets (FMDs) in delaying cancer onset, providing cellular protection and regulating immunity. My project investigates immune profiles, before and after the transfer of donor–derived immune cells previously exposed to fasting, either independently or combined with therapeutic drugs. We aim to identify immune populations, enhanced by this combined treatment, and to recognize their impact on tumor advancement and immune activation. Using the syngeneic 4T1, triple negative breast cancer mouse model, we evaluated how fasting and chemotherapy affect tumor growth and immune competence. Flow cytometry and immunohistochemistry were used to characterize immune cells, recruited at tumors, spleens and bone marrows of treated hosts. A subpopulation of preconditioned splenocytes and tumor-infiltrating lymphocytes, recognized through immunophenotyping, were transplanted into tumor–bearing recipients to assess tumor control, immune priming and cytotoxicity. We observed reduced tumor volume, delayed progression and increased survival rate in the transplants exposed to FMD and doxorubicin. The treatment preserved the size, morphology, and cellularity of healthy, primary and secondary lymphoid organs, while expanded beneficial, antitumor immune signatures. Integrating FMD with standard therapeutic strategies could enhance antitumor immunity and broaden the spectrum of malignancies that respond effectively. Exploring the underlying mechanisms may reveal immune pathways that can be therapeutically leveraged to eradicate tumors, in a field that currently remains unexplored.