A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics.

Cancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Epidemiological studies have further demonstrated the efficacy of antibiotic therapy on the probability of patients' response to ICIs and predictability of the short-term survival of cancer patients. Disturbance to the intestinal microbiota significantly affects ICIs-mediated immune reconstitution and is considered a possible mechanism underlying the development of adverse effects during antibiotic-based ICIs treatment. Intestinal microbiota, antibiotics, and ICIs have gradually become important considerations for the titer of immunotherapy. In the case of immunotherapy, the rational use of antibiotics and intestinal microbiota is expected to yield a better prognosis for patients with malignant tumors.

Zhang J ，Dai Z ，Yan C ，Zhang W ，Wang D ，Tang D ... -  《-》

Modulation of Gut Microbiota to Enhance Effect of Checkpoint Inhibitor Immunotherapy.

Accumulating evidence demonstrated the crucial role of gut microbiota in many human diseases, including cancer. Checkpoint inhibitor therapy has emerged as a novel treatment and has been clinically accepted as a major therapeutic strategy for cancer. Gut microbiota is related to cancer and the effect of immune checkpoint inhibitors (ICIs), and supplement with specific bacterial species can restore or enhance the responses to the ICIs. Namely, specified bacteria can serve as the biomarkers for distinguishing the patient who will respond to ICIs and determine the effectiveness of ICIs, as well as predicting the efficacy of checkpoint inhibitor immunotherapy. Regardless of the significant findings, the relationship between gut microbiota and the effect of ICIs treatment needs a more thorough understanding to provide more effective therapeutic plans and reduce treatment complication. In this review, we summarized the role of gut microbiota played in immune system and cancer. We mainly focus on the relationship between gut microbiota and the checkpoint inhibitor immunotherapy.

Wu J ，Wang S ，Zheng B ，Qiu X ，Wang H ，Chen L ... -  《Frontiers in Immunology》

Modulatory effects of gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors.

The human gastrointestinal (GI) tract harbors gut microbiome, which plays a crucial role in preserving homeostasis at the intestinal host-microbial interface. Conversely, specific gut microbiota may be altered during various pathological conditions and produce a number of toxic compounds and oncoproteins, in turn, to induce both inflammatory response and carcinogenesis. Recently, promising findings have been documented toward the implementation of certain intestinal microbiome in the next era of cancer biology and cancer immunotherapy. Notably, intestinal microbiota can cooperate with immune checkpoint inhibitors (ICIs) of its host, especially in enhancing the efficacy of programmed death 1 (PD-1) protein and its ligand programmed death ligand 1 (PD-L1) blockade therapy for cancer. Herein, we review the dual function of gut microbiota in triggering GI cancers, its association with host immunity and its beneficial functions in modulation of cancer immunotherapy responses. Furthermore, we consider the significance of gut microbiota as a potential biomarker for predicting the efficacy of cancer immunotherapy. Finally, we summarize the relevant limitations that affect the effectiveness and clinical applications of gut microbiome in response to immunotherapy.

Rezasoltani S ，Yadegar A ，Asadzadeh Aghdaei H ，Reza Zali M ... -  《Cancer Medicine》

Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer.

Hayase E ，Jenq RR 《Genome Medicine》

The Challenge of ICIs Resistance in Solid Tumours: Could Microbiota and Its Diversity Be Our Secret Weapon?

The human microbiota and its functional interaction with the human body were recently returned to the spotlight of the scientific community. In light of the extensive implementation of newer and increasingly precise genome sequencing technologies, bioinformatics, and culturomic, we now have an extraordinary ability to study the microorganisms that live within the human body. Most of the recent studies only focused on the interaction between the intestinal microbiota and one other factor. Considering the complexity of gut microbiota and its role in the pathogenesis of numerous cancers, our aim was to investigate how microbiota is affected by intestinal microenvironment and how microenvironment alterations may influence the response to immune checkpoint inhibitors (ICIs). In this context, we show how diet is emerging as a fundamental determinant of microbiota's community structure and function. Particularly, we describe the role of certain dietary factors, as well as the use of probiotics, prebiotics, postbiotics, and antibiotics in modifying the human microbiota. The modulation of gut microbiota may be a secret weapon to potentiate the efficacy of immunotherapies. In addition, this review sheds new light on the possibility of administering fecal microbiota transplantation to modulate the gut microbiota in cancer treatment. These concepts and how these findings can be translated into the therapeutic response to cancer immunotherapies will be presented.

Roberto M ，Carconi C ，Cerreti M ，Schipilliti FM ，Botticelli A ，Mazzuca F ，Marchetti P ... -  《Frontiers in Immunology》