The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide

Abstract

Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate anti-tumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram+ bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of “pathogenic” T helper 17 (pTh17) cells and memory Th1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram+ bacteria showed a reduction in pTh17 responses and their tumors were resistant to cyclophosphamide. Adoptive transfer of pTh17 cells partially restored the anti-tumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.

Bacterial snack attack deactivates a drug

“…Inter actions between bacteria and immune cells are essential for the efficacy of chemotherapeutic agents including cyclophosphamide, oxali platin and cisplatin [9][10][11] , and for immunotherapy approaches that boost the cancer-targeting activity of the immune system 12,13 . Geller and colleagues' work now adds another perspective to the effects of microbes on therapy, by instead demonstrating that bacteria might prevent a treatment from working.…”

Data analysis meets quantum physics

“…This process enables genomic DNA and its associated histone proteins, together known as chromatin, to escape from the nucleus into the cytoplasm 9 …”

Microbiote intestinal et réponses aux thérapies anti-tumorales

“…En effet, des études épidémio-logiques associent le développement d'infections intra-abdominales [25]. L'immunisation antibactérienne implique des lymphocytes effecteurs CD4 + pTh17, appelés « Th17 pathogéniques », qui secrètent à la fois de l'IL-17 et de l'interféron IFN  et des lymphocytes mémoires de polarité Th1 qui aident les lymphocytes anti-tumoraux au contrôle de tumeurs sous-cutanées murines (sarcomes et mastocytomes) ou pulmonaires spontanées (adénocarcinomes mutés sur K-ras et p53).…”