Good bacteria help fight cancer: Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila . Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer. Science , this issue p. 91 , p. 104 , p. 97 ; see also p. 32

Profiling tumor bacteria: Bacteria are well-known residents in human tumors, but whether their presence is advantageous to the tumors or to the bacteria themselves has been unclear. As an initial step toward addressing this question, Nejman et al. produced an exhaustive catalog of the bacteria present in more than 1500 human tumors representing seven different tumor types (see the Perspective by Atreya and Turnbaugh). They found that the bacteria within tumors were localized within both cancer cells and immune cells and that the bacterial composition varied according to tumor type. Certain biologically plausible associations were identified. For example, breast cancer subtypes characterized by increased oxidative stress were enriched in bacteria that produce mycothiol, which can detoxify reactive oxygen species. Science , this issue p. 973 ; see also p. 938

Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2′,2′-difluorodeoxycytidine) into its inactive form, 2′,2′-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDD_L), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDD_L expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria.

New fecal microbiota for cancer patients: The composition of the gut microbiome influences the response of cancer patients to immunotherapies. Baruch et al. and Davar et al. report first-in-human clinical trials to test whether fecal microbiota transplantation (FMT) can affect how metastatic melanoma patients respond to anti–PD-1 immunotherapy (see the Perspective by Woelk and Snyder). Both studies observed evidence of clinical benefit in a subset of treated patients. This included increased abundance of taxa previously shown to be associated with response to anti–PD-1, increased CD8 ⁺ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells, which are involved in immunosuppression. These studies provide proof-of-concept evidence for the ability of FMT to affect immunotherapy response in cancer patients. Science , this issue p. 602 , p. 595 ; see also p. 573