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》

Modulation of gut microbiota to overcome resistance to immune checkpoint blockade in cancer immunotherapy.

Immune checkpoint blockade therapies that target CTLA-4 and PD-1/PD-L1 have ushered in a new era of cancer treatment. Nevertheless, a significant proportion of patients demonstrated primary or acquired resistance. Harnessing gut microbiota has been an emerging novel therapeutic strategy to overcome resistance. Here we summarized the current research status of gut microbiota in immune checkpoint blockade therapies, clinical trials, underlying mechanisms and challenges of microbiome research in checkpoint immunotherapy. Findings from preclinical models, standardized microbiome analysis and progress of multi-omic approaches may better disclose the interaction between gut microbiota and immune checkpoint inhibitors (ICIs) and traditional Chinese medicine can be a potential microbiome modulator to sensitize the response to ICIs.

Huang J ，Jiang Z ，Wang Y ，Fan X ，Cai J ，Yao X ，Liu L ，Huang J ，He J ，Xie C ，Wu Q ，Cao Y ，Leung EL ... -  《-》

Modulation of Gut Microbiota: A Novel Paradigm of Enhancing the Efficacy of Programmed Death-1 and Programmed Death Ligand-1 Blockade Therapy.

Wang Y ，Ma R ，Liu F ，Lee SA ，Zhang L ... -  《Frontiers in Immunology》

The gut microbiota improves the efficacy of immune-checkpoint inhibitor immunotherapy against tumors: From association to cause and effect.

Immune-checkpoint inhibitors (ICIs), including anti-PD-1/PD-L1 therapeutic antibodies, have markedly enhanced survival across numerous cancer types. However, the limited number of patients with durable benefits creates an urgent need to identify response biomarkers and to develop novel strategies so as to improve response. It is widely recognized that the gut microbiome is a key mediator in shaping immunity. Additionally, the gut microbiome shows significant potential in predicting the response to and enhancing the efficacy of ICI immunotherapy against cancer. Recent studies encompassing mechanistic analyses and clinical trials of microbiome-based therapy have shown a cause-and-effect relationship between the gut microbiome and the modulation of the ICI immunotherapeutic response, greatly contributing to the establishment of novel strategies that will improve response and overcome resistance to ICI treatment. In this review, we outline the current state of research advances and discuss the future directions of utilizing the gut microbiome to enhance the efficacy of ICI immunotherapy against tumors.

Xia L ，Zhu X ，Wang Y ，Lu S ... -  《-》

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》