We studied the effects of gut microbiome depletion by oral antibiotics on tumor growth in subcutaneous and liver metastases models of pancreatic cancer, colon cancer, and melanoma. Gut microbiome depletion significantly reduced tumor burden in all the models tested. However, depletion of gut microbiome did not reduce tumor growth in Rag1-knockout mice, which lack mature T and B cells. Flow cytometry analyses demonstrated that gut microbiome depletion led to significant increase in interferon gamma-producing T cells with corresponding decrease in interleukin 17A and interleukin 10-producing T cells. Our results suggest that gut microbiome modulation could emerge as a novel immunotherapeutic strategy.

In studies of mice and cell lines, we found that NFκB activity in PSCs promotes tumor growth by increasing expression of CXCL12, which prevents cytotoxic T cells from infiltrating the tumor and killing cancer cells. Strategies to block CXCL12 in pancreatic tumor cells might increase antitumor immunity.

PURPOSE: We determined if a high-intensity aerobic exercise program would be safe, improve expected fitness and clinical outcomes, and alter exploratory phosphorous magnetic resonance spectroscopy (31 P MRS) outcomes in persons with multiple sclerosis (PwMS). METHODS: This open-label prospective pilot study compared 2 cohorts of ambulatory PwMS matched for age, sex and VO 2 max. Cohorts underwent 8-weeks of high-intensity aerobic exercise (MS-Ex, n=10) or guided stretching (MS-Ctr, n=7). Aerobic exercise consisted of four 30-minute sessions per week while maintaining ≥70% maximal heart rate. Changes in cardiorespiratory fitness, clinical outcomes, and 31 P MRS of tibialis anterior muscle (TA) and brain were compared. Cross-sectional 31 P MRS comparisons were made between all MS participants and a separate matched healthy control (HC) population. RESULTS: The MS-Ex cohort achieved target increases in VO 2 max (mean +12.7%, p=<0.001, between-group improvement p=0.03). One participant was withdrawn for exercise-induced syncope. The MS-Ex cohort had within-group improvements in fat mass (−5.8%, p=0.04), lean muscle mass (+2.6%, p=0.02), Symbol Digit Modalities Test (+15.1%, p=0.04), and cognitive subscore of the Modified Fatigue Impact Scale (MFIS: −26%, p=0.03) while only the physical subscore of the MFIS improved in MS-Ctr (−16.1%, p=0.007). 31 P MRS revealed significant within-group increases in MS-Ex participants in TA rate-constant of PCr recovery (k PCr ; +31.5%, p=0.03) and ATP/PCr (+3.2%, p=0.01), and near significant between-group increases in TA k PCr (p=0.05) but no significant changes in brain 31 P MRS following exercise. Cross-sectional differences existed between MS and HC brain PCr/Pi (4.61 ± 0.44, 3.93 ± 0.19 p=0.0019).