Nod1 promotes colorectal carcinogenesis by regulating the immunosuppressive functions of tumor-infiltrating myeloid cells

Maisonneuve, Charles; Tsang, Derek; Foerster, Elisabeth G.; Robert, Lukian Maxence; Mukherjee, Tapas; Prescott, David; Tattoli, Ivan; Lemire, Paul; Winer, Daniel A.; Winer, Shawn; Streutker, Catherine; Geddes, Kaoru; Cadwell, Ken; Ferrero, Richard L.; Martín, Alberto; Girardin, Stephen E.; Philpott, Dana J.

doi:10.1016/j.celrep.2020.108677

Cited by 54 publications

(47 citation statements)

References 88 publications

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“…TAMs inhibit T cell proliferation through arginine metabolism regulated by arginase1, iNOS, and oxygen or nitrogen radicals [29,91,92]. TAMs directly inhibit CD8 + T cell cytotoxicity through myeloid-specific NOD1 signaling via the release of arginase 1, which promotes immunosuppression and the tumor-permissible tissue microenvironment in CRC development [17,93]. TAMs produce IL-10, which can suppress CD8 + T cell activation by decreasing CD8 protein and T cell receptor colocalization [94].…”

Section: Tams Regulate Immunity In Tme Of Crcmentioning

confidence: 99%

Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis

Wang

Tian

Zhang

2021

IJMS

194

104

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Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor cell microenvironment. As accumulating evidence has shown, tumor-associated macrophages (TAMs)—as abundant and active infiltrated inflammatory cells in the tumor microenvironment (TME)—play a crucial role in CRC. This review focuses on the different mechanisms of TAM in CRC, including switching of phenotypical subtypes; promoting tumor proliferation, invasion, and migration; facilitating angiogenesis; mediating immunosuppression; regulating metabolism; and interacting with the microbiota. Although controversy remains in clinical evidence regarding the role of TAMs in CRC, clarifying their significance in therapy and the prognosis of CRC may shed new light on the optimization of TAM-centered approaches in clinical care.

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Section: Tams Regulate Immunity In Tme Of Crcmentioning

confidence: 99%

Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis

Wang

Tian

Zhang

2021

IJMS

194

104

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“…They exist in almost all body fluids and part of a new type of communication system between cells. The system can carry various cellular molecules that can regulate the physiological morphology of cells and is also closely related to the occurrence of various diseases [4]. Studies have found that tumor derived exosomes can directly inhibit the proliferation of CD8+ T cells, the production of cytokines and cytotoxicity [5].…”

Section: Introductionmentioning

confidence: 99%

The Importance of Exosomal PD-L1 in Cancer Progression and Its Potential as a Therapeutic Target

Zhu

Chen

et al. 2021

Cells

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Binding of programmed cell death ligand 1 (PD-L1) to its receptor programmed cell death protein 1 (PD-1) can lead to the inactivation of cytotoxic T lymphocytes, which is one of the mechanisms for immune escape of tumors. Immunotherapy based on this mechanism has been applied in clinic with some remaining issues such as drug resistance. Exosomal PD-L1 derived from tumor cells is considered to play a key role in mediating drug resistance. Here, the effects of various tumor-derived exosomes and tumor-derived exosomal PD-L1 on tumor progression are summarized and discussed. Researchers have found that high expression of exosomal PD-L1 can inhibit T cell activation in in vitro experiments, but the function of exosomal PD-L1 in vivo remains controversial. In addition, the circulating exosomal PD-L1 has high potential to act as an indicator to evaluate the clinical effect. Moreover, therapeutic strategy targeting exosomal PD-L1 is discussed, such as inhibiting the biogenesis or secretion of exosomes. Besides, some specific methods based on the strategy of inhibiting exosomes are concluded. Further study of exosomal PD-L1 may provide an effective and safe approach for tumor treatment, and targeting exosomal PD-L1 by inhibiting exosomes may be a potential method for tumor treatment.

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“…Except for the microorganisms and metabolites mentioned above, other less investigated bacteria, fungi, archaea, viruses, and metabolites synthesized de novo by gut microbes also influence the host (reviewed elsewhere [10,13]). To give an example, Nod1 stimulation by bacterial peptidoglycan-derived muramyl peptides (MPs) induced monocytic MDSCs infiltration and TAM, which drove carcinogenesis in AOM/DSS treated mice and Apc Min/+ mice [159]. The latest studies uncovered that Streptococcus thermophilus and Faecalibaculum rodentium exerted anti-cancer effects by their metabolites, which reminds us that the role of the bacteria and their metabolites strongly reduced during carcinogenesis is worth exploring to seek therapy opportunity [32,160].…”

Section: Discussionmentioning

confidence: 99%

Microbiota-Associated Metabolites and Related Immunoregulation in Colorectal Cancer

Chen

2021

Cancers

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A growing body of research has found close links between the human gut microbiota and colorectal cancer (CRC), associated with the direct actions of specific bacteria and the activities of microbiota-derived metabolites, which are implicated in complex immune responses, thus influencing carcinogenesis. Diet has a significant impact on the structure of the microbiota and also undergoes microbial metabolism. Some metabolites, such as short-chain fatty acids (SCFAs) and indole derivatives, act as protectors against cancer by regulating immune responses, while others may promote cancer. However, the specific influence of these metabolites on the host is conditional. We reviewed the recent insights on the relationships among diet, microbiota-derived metabolites, and CRC, focusing on their intricate immunomodulatory responses, which might influence the progression of colorectal cancer.

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Nod1 promotes colorectal carcinogenesis by regulating the immunosuppressive functions of tumor-infiltrating myeloid cells

Cited by 54 publications

References 88 publications

Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis

Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis

The Importance of Exosomal PD-L1 in Cancer Progression and Its Potential as a Therapeutic Target

Microbiota-Associated Metabolites and Related Immunoregulation in Colorectal Cancer

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