Impact of gut microbiome in the development and treatment of pancreatic cancer: Newer insights.

The gut microbiome plays an important role in the variation of pharmacologic response. This aspect is especially important in the era of precision medicine, where understanding how and to what extent the gut microbiome interacts with drugs and their actions will be key to individualizing therapy. The impact of the composition of the gut microbiome on the efficacy of newer cancer therapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell treatment has become an active area of research. Pancreatic adenocarcinoma (PAC) has a poor prognosis even in those with potentially resectable disease, and treatment options are very limited. Newer studies have concluded that there is a synergistic effect for immunotherapy in combination with cytotoxic drugs, in the treatment of PAC. A variety of commensal microbiota can affect the efficacy of conventional chemotherapy and immunotherapy by modulating the tumor microenvironment in the treatment of PAC. This review will provide newer insights on the impact that alterations made in the gut microbial system have in the development and treatment of PAC.

Bangolo AI ，Trivedi C ，Jani I ，Pender S ，Khalid H ，Alqinai B ，Intisar A ，Randhawa K ，Moore J ，De Deugd N ，Faisal S ，Suresh SB ，Gopani P ，Nagesh VK ，Proverbs-Singh T ，Weissman S ... -  《-》

The Gut Microbiome and Pancreatic Cancer Development and Treatment.

Changes in the gut microbiome have been increasingly shown to accompany oncogenesis across various tumors. Similarly, microbial dysbiosis was found to be associated with pancreatic cancer progression and survival outcomes, expanding the field of tumor microenvironment research in pancreatic cancer. Mechanistic studies in pancreatic cancer models implicate components of the gut and pancreatic cancer microbiome in regulating tumorigenesis by altering cancer cell signaling, modulating immune function, and influencing the efficacy of current therapies in pancreatic cancer. This review discusses the outcomes of microbial modulation across various preclinical and clinical studies and highlights ongoing trials targeting the microbiome for pancreatic cancer therapy.

Attebury H ，Daley D 《-》

Unraveling the gut microbiome's contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives.

The gut microbiome plays a significant role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), influencing oncogenesis, immune responses, and treatment outcomes. Studies have identified microbial species like Porphyromonas gingivalis and Fusobacterium nucleatum, that promote PDAC progression through various mechanisms. Additionally, the gut microbiome affects immune cell activation and response to immunotherapy, including immune checkpoint inhibitors and CAR-T therapy. Specific microbes and their metabolites play a significant role in the effectiveness of immune checkpoint inhibitors (ICIs). Alterations in the gut microbiome can either enhance or diminish responses to PD-1/PD-L1 and CTLA-4 blockade therapy. Additionally, bacterial metabolites like trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS) impact antitumor immunity, offering potential targets to augment immunotherapy responses. Modulating the microbiome through fecal microbiota transplantation, probiotics, prebiotics, dietary changes, and antibiotics shows promise in PDAC treatment, although outcomes are highly variable. Dietary modifications, particularly high-fiber diets and specific fat consumption, influence microbiome composition and impact cancer risk. Combining microbiome-based therapies with existing treatments holds potential for improving PDAC therapy outcomes, but further research is needed to optimize their effectiveness.

Tabrizi E ，Pourteymour Fard Tabrizi F ，Mahmoud Khaled G ，Sestito MP ，Jamie S ，Boone BA ... -  《Frontiers in Immunology》

The Potential of the Gut Microbiome to Reshape the Cancer Therapy Paradigm: A Review.

Liu L ，Shah K 《-》

Exploring the Emerging Role of the Gut Microbiota and Tumor Microenvironment in Cancer Immunotherapy.

The tumor microenvironment (TME) is a complex ecosystem, which includes many different types of cells, abnormal vascular systems, and immunosuppressive cytokines. TME serves an important function in tumor tolerance and escapes from immune surveillance leading to tumor progression. Indeed, there is increasing evidence that gut microbiome is associated with cancer in a variety of ways, as specific microbial signatures are known to promote cancer development and influence safety, tolerability, and efficacy of therapies. Studies over the past five years have shown that the composition of the intestinal microbiota has a significant impact on the efficacy of anticancer immunosurveillance, which contribute to the therapeutic activity of cancer immunotherapies based on targeting cytotoxic T lymphocyte protein 4 (CTLA-4) or programmed cell death protein 1 (PD-1)-programmed cell death 1 ligand 1 (PD-L1) axis. In this review, we mainly discuss the impact of TME on cancer and immunotherapy through immune-related mechanisms. We subsequently discuss the influence of gut microbiota and its metabolites on the host immune system and the formation of TME. In addition, this review also summarizes the latest research on the role of gut microbiota in cancer immunotherapy.

Qiu Q ，Lin Y ，Ma Y ，Li X ，Liang J ，Chen Z ，Liu K ，Huang Y ，Luo H ，Huang R ，Luo L ... -  《Frontiers in Immunology》