The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

By S. Viaud, F. Saccheri, G. Mignot, T. Yamazaki, Romain Daillère, D. Hannani, D. Enot, C. Pfirschke, Camilla Engblom, M. Pittet and 23 more. Science, 2013

1,872 citations recorded by the source corpus.

The Microbiota Makes for Good Therapy The gut microbiota has been implicated in the development of some cancers, such as colorectal cancer, but—given the important role our intestinal habitants play in metabolism—they may also modulate the efficacy of certain cancer therapeutics. Iida et al. (p. 967) evaluated the impact of the microbiota on the efficacy of an immunotherapy [CpG (the cytosine, guanosine, phosphodiester link) oligonucleotides] and oxaliplatin, a platinum compound used as a chemotherapeutic. Both therapies were reduced in efficacy in tumor-bearing mice that lacked microbiota, with the microbiota important for activating the innate immune response against the tumors. Viaud et al. (p. 971) found a similar effect of the microbiota on tumor-bearing mice treated with cyclophosphamide, but in this case it appeared that the microbiota promoted an adaptive immune response against the tumors. The gut microbiota promote the efficacy of several antineoplastic agents in mice. Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor 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-positive 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-positive bacteria showed a reduction in pTH17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pTH17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.

Subfields: Biological Psychiatry, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5d6c3ee44871dc8942f49ac5a1b1e04b5ff2d29d

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In Biological Psychiatry

1. W. Zou
2. Y. Belkaid

In Genetics

1. G. Núñez
2. W. Zou
3. Oliver Kepp
4. Guido Kroemer
5. Rob Knight
6. Jeff Hasty
7. T. Kanai
8. L. Zitvogel

In Molecular Biology

1. Guido Kroemer
2. L. Galluzzi
3. Oliver Kepp
4. L. Zitvogel
5. P. Allavena
6. M. Zeng
7. Y. Belkaid
8. W. Zou

Citations in the corpus

• Cellular Senescence: Aging, Cancer, and Injury. (2019, background): “Moreover, increasing evidence shows that the microbiota is important for the efficacy of both classical chemotherapy (328) and of immune checkpoint inhibitors (anti–PD-L1, anti–CTLA-4, and anti-PD1) (298, 327).”
• The microbiome and cancer (2018, background): “The efficacy of cyclophosphamide has also been shown to be dependent on the microbiome, in this case working through an immunological mechanism [86].”
• Impacts of Gut Bacteria on Human Health and Diseases (2015, background): “The results suggested that the gut bacteria may help shape the anticancer immune response [107].”
• PD-L1 (B7-H1) and PD-1 Pathway Blockade for Cancer Therapy: Mechanisms, Response Biomarkers and Combinations (2016, background): “Chemotherapyinduced TH1 and TH17 responses are enhanced by translocating commensals and contribute to tumor eradication (98, 99).”