Low-Dose Alcohol-Induced Inhibition of Mouse Orthotopically Transplanted Tumors Is Associated with T-Cell Response

Abstract

<b><i>Introduction:</i></b> The effects of low-dose alcohol consumption on colorectal cancer development are not well understood. Epidemiological studies have reported that people who consume small amounts of alcohol have lower mortality rates than both nondrinkers and heavy drinkers. This phenomenon has been labeled the “J-curve effect” of alcohol. This study examined the effects of low-dose alcohol (0.5%, 1%, and 2%) on tumor growth in a transplant colon cancer model. <b><i>Methods:</i></b> BALB/c and BALB/c nude mice were used to analyze T-cell immunity. Syngeneic CT26 murine colon cancer cells were implanted into the cecal wall, and the resulting T-cell immune effects were monitored. <b><i>Results:</i></b> The growth of orthotopic tumors was markedly inhibited upon ingestion of low-dose (0.5%) alcohol compared with that in the control mice. In contrast, cells from the same line were injected into the cecal wall of nude mice, and tumor growth inhibition was not observed. Histopathological and RNA sequence analyses were performed to elucidate the mechanisms underlying tumor growth inhibition. An increase in tumor CD8⁺ T lymphocytes and changes in cytokine levels were observed. Microbiome analysis using 16S rRNA gene sequencing of cecal contents was performed and revealed <i>Mucispirillum schaedleri</i> and <i>Clostridium cocleatum</i> showed decreased and increased abundance, respectively, in the alcohol group. <b><i>Discussion/Conclusion:</i></b> Ingesting a threshold amount of alcohol results in the infiltration of T lymphocytes, which may enhance immune responsiveness in mouse colorectal cancer models.