Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated “hot” tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts “cold” tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.

Epidemiological studies propose a protective role for dietary fiber in colon cancer (CRC). One possible mechanism of fiber is its fermentation property in the gut and ability to change microbiota composition and function. Here, we investigate the role of a dietary fiber mixture in polyposis and elucidate potential mechanisms using TS4Cre × cAPCl°x468 mice. Stool microbiota profiling was performed, while functional prediction was done using PICRUSt. Stool short-chain fatty acid (SCFA) metabolites were measured. Histone acetylation and expression of SCFA butyrate receptor were assessed. We found that SCFA-producing bacteria were lower in the polyposis mice, suggesting a decline in the fermentation product of dietary fibers with polyposis. Next, a high fiber diet was given to polyposis mice, which significantly increased SCFA-producing bacteria as well as SCFA levels. This was associated with an increase in SCFA butyrate receptor and a significant decrease in polyposis. In conclusion, we found polyposis to be associated with dysbiotic microbiota characterized by a decline in SCFA-producing bacteria, which was targetable by high fiber treatment, leading to an increase in SCFA levels and amelioration of polyposis. The prebiotic activity of fiber, promoting beneficial bacteria, could be the key mechanism for the protective effects of fiber on colon carcinogenesis. SCFA-promoting fermentable fibers are a promising dietary intervention to prevent CRC.

Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the third most common cancer diagnosed in both men and women in the world. Several environmental and habitual factors have been associated with the CRC risk. Alcohol intake, a common and rising habit of modern society, is one of the major risk factors for development of CRC. Here, we will summarize the evidence linking alcohol with colon carcinogenesis and possible underlying mechanisms. Some epidemiologic studies suggest that even moderate drinking increases the CRC risk. Metabolism of alcohol involves ethanol conversion to its metabolites that could exert carcinogenic effects in the colon. Production of ethanol metabolites can be affected by the colon microbiota, another recently recognized mediating factor to colon carcinogenesis. The generation of acetaldehyde and alcohol’s other metabolites leads to activation of cancer promoting cascades, such as DNA-adduct formation, oxidative stress and lipid peroxidation, epigenetic alterations, epithelial barrier dysfunction, and immune modulatory effects. Not only does alcohol induce its toxic effect through carcinogenic metabolites, but alcoholics themselves are predisposed to a poor diet, low in folate and fiber, and circadian disruption, which could further augment alcohol-induced colon carcinogenesis.

Colorectal cancer (CRC) is one of the most diagnosed cancers in the world. Even though screening, surgery and oncology have greatly advanced, CRC is still one of the leading causes of cancer deaths, with 700,000 annual mortalities in both men and women. Environmental and lifestyle factors brought up by industrialization, such as an altered diet, lack of physical activity, increase in alcohol consumption, and circadian disruption, have greatly affected the burden of CRC. These factors increase the CRC risk, at least partly, by pathologically altering the colonic environment, including composition of the gut microbiota, referred to as dysbiosis. Colonic dysbiosis can promote pro-carcinogenic immune signaling cascades, leading to pro-tumorigenic inflammation, carcinogen production, and altered cellular responses in susceptible host resulting to development and/or progression of CRC. Nutraceuticals such as prebiotic molecules and probiotic bacterial species can help maintain intestinal microbial homeostasis and thus mitigate this pathological processes. Therefore, prebiotics and probiotics can hinder the effects of dysbiosis by encouraging anti-carcinogenic, anti-inflammatory immunity, the maintenance of the intestinal epithelial barrier, pro-apoptotic mechanisms, and carcinogen inactivation. In addition to its implications in preventing CRC, because of the mechanisms affected, nutraceuticals are being discovered as potential adjuncts to immune checkpoint inhibitors in the treatment of CRC. In this review, we provide an overview of the potential implications of prebiotics and probiotics in the prevention and treatment of CRC.

No abstract