IMDEA Madrid notes that combination of fasting and chemotherapy improves response against cancer

Team research from IMDEA Food Institute demonstrated positive immunological effects of fasting along with chemotherapy such as doxorubicin or oxaliplatin, although differences in this process are observed by sex, especially in melanoma models and with testosterone as a relevant factor, which has notable clinical implications.

One of the main findings is the identification of “sexual dimorphism” in immune responses caused by a combination of fasting and chemotherapy: after a study in mice, it is more pronounced in males than in females. This phenomenon is noticeable in a melanoma model yet, in another case of colorectal adenocarcinoma, no differences in the response of the two sexes were observed, suggesting a marked complexity in the interaction between treatment and different types of disease.

This finding highlights the importance of considering sex as a critical factor in developing personalized therapeutic strategies to combat cancer. The results show how fasting increases the presence of natural killer cells and natural killer T cells in melanoma and CD8 lymphocytes in colorectal adenocarcinoma when used in conjunction with chemotherapy.

The study expands on previous research from the IMDEA Food Metabolic Syndrome Panel, which has already found the ability of short-term fasting to modulate various new biomarkers associated with protection from chemotherapy toxicity. In other work, they also showed an increase in p21 protein with a combination of fasting and chemotherapy, with two consequences: protection against toxicity in metabolically important tissues (kidneys, liver and heart) and increased effectiveness of treatment of colorectal adenocarcinoma.

This latest work, published in the journal Cancer Communications, was joined by eminent researchers from the Severo Ochoa Center for Molecular Biology (CBM), the National Center for Cancer Research (CNIO) and the University of San Pablo CEU. In addition, he received financial support from the Spanish Cancer Association.

One of the goals of this work was to study how sex influences the effect of combining fasting and chemotherapy in the fight against cancer. To do this, tests were conducted on male and female mice with melanoma.

Molecular biologist Pablo José Fernández Marcos, who led the study, emphasizes that the study reveals what he calls “sexual dimorphism in response to starvation,” which he believes “has significant translational implications, especially in tumors such as melanoma.” , where testosterone, the male sex hormone, plays a critical role in the effects of fasting.”

By studying different cancer models, the researchers observed different immune responses, and therefore, “the benefit of chemotherapy during fasting may not depend on the specific immune cell type.” This is precisely what Dr. Fernandez Marcos points out, who shows that the interactions between immune cells in different tissues, such as the tumor, peripheral blood and nearby lymph nodes, are extremely complex.

In the B16-F10 melanoma model, it was observed that certain cells (natural killer cells and natural killer T cells) were particularly effective when fasting was combined with chemotherapy. In addition, CD8 lymphocytes also play an important role in the differences observed between sexes in this model. On the other hand, in a colon adenocarcinoma model (MC38), the team found an increase in effector CD8 T cells and CD4 Th1 cells in the tumor when fasting and chemotherapy were combined with antitumor properties.

In contrast to the previous melanoma model, there is an enhanced response to fasting. in both male and female mice. In addition, the researchers observed a significant decrease in the number of macrophages in the tumor, which have protumor properties. These results show “the complexity of the immune response across different types of cancer” and suggest that combining fasting and chemotherapy may be a promising strategy to improve the effectiveness of cancer treatments.