Unexpected guests in the tumor microenvironment: microbiome in cancer

Wong-Rolle, Abigail; Wei, Haohan Karen; Zhao, Chen; Jin, Chengcheng

doi:10.1007/s13238-020-00813-8

Cited by 137 publications

(103 citation statements)

References 81 publications

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“…The intratumor microbiome is also an integral part of the TME and may play a critical role in shaping the TME, affecting tumorigenesis, progression, and tumor immunity in the TME and the response to immunotherapy [ 85 ]. Lung cancer is closely associated with local dysbiosis, chronic inflammation, and pulmonary infections.…”

Section: Cxcl8-cxcr1/2 Signaling Pathwaymentioning

confidence: 99%

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Han

Yang

et al. 2021

Molecules

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In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of CXCL8 on individual cell types can result in cascading alterations to the TME. The changes in the TME components such as the cancer-associated fibroblasts (CAFs), the immune cells, the extracellular matrix, the blood vessels, or the lymphatic vessels further influence tumor progression and therapeutic resistance. Emerging roles of the microbiome in tumorigenesis or tumor progression revealed the intricate interactions between inflammatory response, dysbiosis, metabolites, CXCL8, immune cells, and the TME. Studies have shown that CXCL8 directly contributes to TME remodeling, cancer plasticity, and the development of resistance to both chemotherapy and immunotherapy. Further, clinical data demonstrate that CXCL8 could be an easily measurable prognostic biomarker in patients receiving immune checkpoint inhibitors. The blockade of the CXCL8-CXCR1/2 axis alone or in combination with other immunotherapy will be a promising strategy to improve antitumor efficacy. Herein, we review recent advances focusing on identifying the mechanisms between TME components and the CXCL8-CXCR1/2 axis for novel immunotherapy strategies.

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Section: Cxcl8-cxcr1/2 Signaling Pathwaymentioning

confidence: 99%

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Han

Yang

et al. 2021

Molecules

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“…It was demonstrated that microbiota in upper respiratory tract of mice could inhibit excessive lung immune response to acute influenza infection through promoting the differentiation of M2 macrophages (Wang et al, 2013). Although dysbiosis of lung microbiota has been linked to lung cancer, their roles in tumorigenesis and/or progression have not been revealed comprehensively (Wong-Rolle et al, 2021). Recently, Jin et al reported that lung microbiota could promote inflammatory responses and tumor cell proliferation by activating lung-resident gd T cells in mouse models, which established a clearly association between local microbiota-immune crosstalk and cancer development (Jin et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Convergent alteration of lung tissue microbiota and tumor cells in lung cancer

Dong

Tan

et al. 2022

iScience

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Microbiota-host interaction plays an important role in cancer predisposing, initiation, progression, and response to therapy. Here, we explored the composition of lung tissue microbiota in 143 Chinese patients through conducting 16S rRNA gene sequencing, while TP53 mutation in tumor cells was assessed simultaneously. We found PAH-degrading microbes were more abundant in lung tumor microbiota from smokers. Furthermore, TP53 mutation was more prevalent in smokers, and TP53-mutated tumor harbored more Massilia, as well as Acidovorax that was also capable of degrading PAH. Further analysis showed DNA recombination and repair pathway was enriched in microbiota of smokers, which was convergent to the alteration occurred in tumor cells. Meanwhile, the microbiota of TP53-mutated tumor also exhibited dysregulation of p53 signaling pathway. Our results provided insights into the association of lung commensal microbes with tobacco exposure and host gene mutation, suggesting microbiota and tumor cells might undergo convergent alteration and mutually benefit each other.

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“…For example, components of the extracellular matrix, DNA released by apoptotic cells, and heat-shock proteins are potential TLR agonists, the so-called DAMPs [60]. In addition, tumor-associated microbiota [61,62] or bacteria colonizing different tissues [62][63][64] may be continuous sources of microbial products that can stimulate TLRs in immune cells, as described in the peritoneum [65], a common site of metastasis of ovarian cancer [66]. It is possible that even when delivered as a monotherapy, anti-PD-1 antibodies may act on macrophages in which TLR signaling has already been triggered by endogenous ligands, mirroring the biological effects described in the present study.…”

Section: Discussionmentioning

confidence: 99%

Macrophages Impair TLR9 Agonist Antitumor Activity through Interacting with the Anti-PD-1 Antibody Fc Domain

Camelliti

Noci

Bianchi

et al. 2021

Cancers

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Background. A combination of TLR9 agonists and an anti-PD-1 antibody has been reported to be effective in immunocompetent mice but the role of innate immunity has not yet been completely elucidated. Therefore, we investigated the contribution of the innate immune system to this combinatorial immunotherapeutic regimens using an immunodeficient mouse model in which the effector functions of innate immunity can clearly emerge without any interference from T lymphocytes. Methods. Athymic mice xenografted with IGROV-1 human ovarian cells, reported to be sensitive to TLR9 agonist therapy, were treated with cytosine–guanine (CpG)-oligodeoxynucleotides (ODNs), an anti-PD-1 antibody or their combination. Results. We found that PD-1 blockade dampened CpG-ODN antitumor activity. In vitro studies indicated that the interaction between the anti-PD-1 antibody fragment crystallizable (Fc) domain and macrophage Fc receptors caused these immune cells to acquire an immunoregulatory phenotype, contributing to a decrease in the efficacy of CpG-ODNs. Accordingly, in vivo macrophage depletion abrogated the detrimental effect exerted by the anti-PD-1 antibody. Conclusion. Our data suggest that if TLR signaling is active in macrophages, coadministration of an anti-PD-1 antibody can reprogram these immune cells towards a polarization state able to negatively affect the immune response and eventually promote tumor growth.

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Unexpected guests in the tumor microenvironment: microbiome in cancer

Cited by 137 publications

References 81 publications

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Convergent alteration of lung tissue microbiota and tumor cells in lung cancer

Macrophages Impair TLR9 Agonist Antitumor Activity through Interacting with the Anti-PD-1 Antibody Fc Domain

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