4.6 Review

Fungi, host immune response, and tumorigenesis

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00025.2021

关键词

complement system; gut microbiome; immunotherapy; mycobiome; pancreatic cancer

资金

  1. City University of New York Enhanced Research Grant [63814-00 51, NCI CA206105]
  2. DOD [W81XWH-19-1-0605]

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Advances in -omics analyses have improved our understanding of the microbiome's role in human health and disease, particularly in noninfectious diseases like cancer. Research now recognizes the significance of the virome and microbial dysbiosis, with focus on the role of mycobiome in tumorigenesis and interactions with the host's immune response. Studies have shown that microbial intervention in cancer therapy may modify the tumor microenvironment to enhance immune response and eliminate tumorigenesis.
Advances in -omics analyses have tremendously enhanced our understanding of the role of the microbiome in human health and disease. Most research is focused on the bacteriome, but scientists have now realized the significance of the virome and microbial dysbiosis as well, particularly in noninfectious diseases such as cancer. In this review, we summarize the role of mycobiome in tumorigenesis, with a dismal prognosis, and attention to pancreatic ductal adenocarcinoma (PDAC). We also discuss bacterial and mycobial interactions to the host's immune response that is prevalently responsible for resistance to cancer therapy, including immunotherapy. We reported that the Malassezia species associated with scalp and skin infections, colonize in human PDAC tumors and accelerate tumorigenesis via activating the C3 complement-mannose-binding lectin (MBL) pathway. PDAC tumors thrive in an immunosuppressive microenvironment with desmoplastic stroma and a dysbiotic microbiome. Host-microbiome interactions in the tumor milieu pose a significant threat in driving the indolent immune behavior of the tumor. Microbial intervention in multimodal cancer therapy is a promising novel approach to modify an immunotolerant (cold) tumor microenvironment to an immunocompetent (hot) milieu that is effective in eliminating tumorigenesis.

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