Influence of probiotic‑regulated gut microbiota on immune checkpoint blockade therapy

Gao Guangqi, Zhang Heping

Electronic Journal of Metabolism and Nutrition of Cancer ›› 2021, Vol. 8 ›› Issue (2) : 111-117.

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PDF(1020 KB)
Electronic Journal of Metabolism and Nutrition of Cancer ›› 2021, Vol. 8 ›› Issue (2) : 111-117.

Influence of probiotic‑regulated gut microbiota on immune checkpoint blockade therapy

  • Immune checkpoint blockade is a breakthrough technology in tumor immunotherapy. It could be summarized that monoclonal antibodies suppressed the target negative regulators to activate the downstream immune response, which produced a cytotoxic T cell mediated killing effect on tumor cells. However, this treatment can only benefit a part of patients, so it is important to find out effective ways to improve the cancer immunotherapy. Gut microbiota is considered to be an important contribution to the success of checkpoint blockade therapy. Studies showed that the presence, composition, and diversity of gut microbiota directly affected the efficacy of cancer treatment in patients and mice, and the efficiency of the immune response could be improved by fecal microbiota transplantation or beneficial bacteria intervention. There was a significant correlation between the characteristic bacteria or microbiota of intestinal tract and the antigen presentation of dendritic cells in the host tumor microenvironment as well as the activity of effector T lymphocytes. To a large extent, the regulation mechanism between gut microbiota and host immunity is that substances, such as short?chain fatty acids or secondary bile acids, produced by gut bacteria metabolism can regulate the gene expression or the differentiation and activity of immune cells through ligand?receptor pathways. Another possible factor can be supposed as that bacterial translocation into the tumor stimulates the systemic immune response. Based on these gut microbiota?host immune investigations, it can be confirmed that improving or maintaining healthy intestinal microbiota structure by avoiding the use of antibiotics, fecal bacteria transplantation or probiotic intervention is an effective way to optimize the immune checkpoint blockade treatment of tumor.
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Abstract

Immune checkpoint blockade is a breakthrough technology in tumor immunotherapy. It could be summarized that monoclonal antibodies suppressed the target negative regulators to activate the downstream immune response, which produced a cytotoxic T cell mediated killing effect on tumor cells. However, this treatment can only benefit a part of patients, so it is important to find out effective ways to improve the cancer immunotherapy. Gut microbiota is considered to be an important contribution to the success of checkpoint blockade therapy. Studies showed that the presence, composition, and diversity of gut microbiota directly affected the efficacy of cancer treatment in patients and mice, and the efficiency of the immune response could be improved by fecal microbiota transplantation or beneficial bacteria intervention. There was a significant correlation between the characteristic bacteria or microbiota of intestinal tract and the antigen presentation of dendritic cells in the host tumor microenvironment as well as the activity of effector T lymphocytes. To a large extent, the regulation mechanism between gut microbiota and host immunity is that substances, such as short⁃chain fatty acids or secondary bile acids, produced by gut bacteria metabolism can regulate the gene expression or the differentiation and activity of immune cells through ligand⁃receptor pathways. Another possible factor can be supposed as that bacterial translocation into the tumor stimulates the systemic immune response. Based on these gut microbiota⁃host immune investigations, it can be confirmed that improving or maintaining healthy intestinal microbiota structure by avoiding the use of antibiotics, fecal bacteria transplantation or probiotic intervention is an effective way to optimize the immune checkpoint blockade treatment of tumor.

Key words

Gut microbiota / Immune checkpoint blockade / Tumor immunotherapy / Programmed cell death protein?1 / Cytotoxic T lymphocyte?associated antigen?4

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Gao Guangqi, Zhang Heping. Influence of probiotic‑regulated gut microbiota on immune checkpoint blockade therapy[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2021, 8(2): 111-117
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