About this Research Topic
Cellular therapies using CAR-T cells or tumor-infiltrating lymphocytes (TILs) are promising anti-cancer approaches, especially in haematological malignancies. The responses to CAR-T cell therapy and TIL therapy have been variously influenced by several factors including the physiological status of the cells being used, antigen heterogeneity of the tumor cells, complex tumor microenvironment, and the health of the host including the levels of stress hormones. Additionally, host-microbiome has emerged as an important factor that controls the activation status and the longevity of the immune cells. In fact, the impact of secretome, i.e. the soluble substances produced by the gut microbiome, on response to various anti-cancer therapies including immunotherapy is well established. In the current research topic, we envision addressing the role of gut microbiome in influencing the therapeutic outcomes of cellular therapies including CAR-T cell therapy and TIL therapy, especially in the context of solid tumors.
The efficacy of CAR-T cells is extremely limited in solid tumors. Apart from tumor-derived factors such as inhibitory cytokines and immune suppressive cells, host-derived factors such as gut microbiome have started to be identified as an aspect affecting the therapeutic outcomes of immunotherapies. Metabolites produced by gut bacteria, such as short-chain fatty acids (SCFAs), can affect the activity and function of immune cells. These metabolites can either enhance or inhibit the function of immunotherapies, thereby impacting the overall effectiveness of the therapy. However, the full spectrum of effect of gut on CAR-T and other cell-mediated therapies is not defined. Here, we intend to comprehensively address the factors through which the gut microbiome is known to affect immune cells. This would be particularly important to extend our understanding of the mechanisms that influence cell therapies and devise strategies through which their efficacy can be enhanced.
In this research topic, our overall intent is to address the impact of gut microbiome on cell therapies including CAR-T cell and TIL therapy, with a special focus on solid tumors. We welcome original research articles, review articles, and other articles types allowed by the journal.
The major specific themes (questions) being addressed are the following:
1) Impact of the Gut microbiome on the efficacy of CAR-T cells in solid and/or liquid tumors.
2) Gut Microbiome and CAR-T Cell Therapy-Associated Toxicities.
3) Microbiome-Driven Biomarkers for CAR-T Therapy Response
4) Probiotic and Dietary Interventions in Enhancing CAR-T Therapy (role of antibiotics).
5) Gut’s effect on TIL therapy-- speculative based on current literature.
6) Gut Microbiome Modulation to Improve CAR-T Cell Therapy Outcomes
Prof. Vivek Verma is a co-founder of a start-up based in Minneapolis, MN. He also holds a patent for using PKM2 to enhance mitochondrial metabolism in Cd8 T cells. Prof. Leena Hilakivi-Clarke declares no conflicts of interest
The efficacy of CAR-T cells is extremely limited in solid tumors. Apart from tumor-derived factors such as inhibitory cytokines and immune suppressive cells, host-derived factors such as gut microbiome have started to be identified as an aspect affecting the therapeutic outcomes of immunotherapies. Metabolites produced by gut bacteria, such as short-chain fatty acids (SCFAs), can affect the activity and function of immune cells. These metabolites can either enhance or inhibit the function of immunotherapies, thereby impacting the overall effectiveness of the therapy. However, the full spectrum of effect of gut on CAR-T and other cell-mediated therapies is not defined. Here, we intend to comprehensively address the factors through which the gut microbiome is known to affect immune cells. This would be particularly important to extend our understanding of the mechanisms that influence cell therapies and devise strategies through which their efficacy can be enhanced.
In this research topic, our overall intent is to address the impact of gut microbiome on cell therapies including CAR-T cell and TIL therapy, with a special focus on solid tumors. We welcome original research articles, review articles, and other articles types allowed by the journal.
The major specific themes (questions) being addressed are the following:
1) Impact of the Gut microbiome on the efficacy of CAR-T cells in solid and/or liquid tumors.
2) Gut Microbiome and CAR-T Cell Therapy-Associated Toxicities.
3) Microbiome-Driven Biomarkers for CAR-T Therapy Response
4) Probiotic and Dietary Interventions in Enhancing CAR-T Therapy (role of antibiotics).
5) Gut’s effect on TIL therapy-- speculative based on current literature.
6) Gut Microbiome Modulation to Improve CAR-T Cell Therapy Outcomes
Prof. Vivek Verma is a co-founder of a start-up based in Minneapolis, MN. He also holds a patent for using PKM2 to enhance mitochondrial metabolism in Cd8 T cells. Prof. Leena Hilakivi-Clarke declares no conflicts of interest
Keywords: Gut microbiome, Cancer immunotherapy, CAR-T cells, tumors, TILs, Therapy resistance
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