In 1981, neoplasms became the primary cause of death in Japan, and the upward trend as a cause of death remains intact even now. In 2018, approximately 374,000 Japanese were killed by cancers, the proportion of total deaths being 27.4%. This means that approximately one out of 3.5 deaths in Japan were caused by neoplasms. In recent years, immunotherapies have rapidly developed and been now recognized as the “fourth” standard therapy against cancer, after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitor therapies have been attracting attention because of their potent clinical efficacies against advanced cancers. Several antibodies for immune checkpoint blockade have been approved as clinical drugs in many countries, including Japan, and a large number of clinical trials are currently proceeding to further expand their applications. However, there remain several critical issues in the present immune checkpoint blockade therapy, one of which is the identification of biomarkers correlating with either clinical benefits or adverse events. In this review, we discuss recent findings concerning the relationships between enteric microbiota and the clinical efficacy/inefficacy of immune checkpoint blockade therapies.

Breast cancer is the most common cancer among women, and the lifetime risk of the disease continues to increase every year in Japan. Treatment is based on the subtype classifications of Luminal A, Luminal B, Her2-enriched, and triple-negative, which are characterized by estrogen, progesterone, and HER2 receptors, Ki67, and histological grade. Risk factors for breast cancer include genetic factors, hormone replacement therapy, lifestyle, diet, age, age at menarche and menopause, and mammary gland density, and other risk factors, including regional and racial differences. However, these factors do not explain all cases of breast cancer. In recent years, the human microbiota has attracted much attention in various fields, including tumor biology. A dynamic and highly complex network exists between the human host and the microbiota, which is involved in regulating a variety of signaling pathways, including the E-cadherin- β -catenin pathway, DNA double-strand breaks, promotion of apoptosis, and induction of inflammatory signaling pathways through interaction with changes in cell differentiation. The interaction between the human microbiome and cancer is referred to as the “oncobiome,” and the human host is also believed to influence the microbiota and its mechanisms. In breast cancer, the link to Intestinal bacteria is gaining attention, and both pre-clinical and clinical types of research have been conducted. The microbiome is a risk factor for breast cancer and has also been associated with the therapeutic effects of drugs. It has been suggested that disruption of the commensal microbiota may lead to an imbalance in the microbiota, which in turn may lead to the development of cancer. It has also been reported that there are differences between healthy individuals and breast cancer patients in the constituent flora and abundance of the microbiome in breast tissue. In this section, we will discuss intestinal bacteria and breast cancer based on recent findings and future prospects.

Human intestinal flora plays an important role in health maintenance, however, in recent years, it has been said that dysbiosis is increasing among Japanese people due to changes in eating habits or greater social stress. In general, sending living lactic acid bacteria to the intestine is thought to be an efficient way of improving dysbiosis, and some lactic acid bacteria, commonly known as plant- origin lactic acid bacteria, are expected to withstand the harsh environment of the digestive tract and reach the intestines. In this study, we investigated the effect of long-term intake of the supplement MP-1, which contains lactic acid bacteria isolated from the Tonewase persimmon, on the intestinal flora of mice. The mice were divided into three groups. The MP-1 and control groups were respectively fed tablets with and without MP-1 together with a regular diet, and the remaining group was fed only a regular diet for 28 days. In the fecal flora of the MP-1 group, lactic acid bacteria that were not detected before the experiment were detected on day 28. On the other hand, no significant changes were observed in fecal flora of the control and regular diet groups. Therefore, we concluded that long-term intake of MP-1, a supplement containing lactic acid bacteria isolated from the Tonewase persimmon, had a notable effect on their intestinal flora.