Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche

Plebanek, Michael P.; Angeloni, Nicholas L.; Vinokour, Elena; Li, Jia; Henkin, Anna; Martinez-Marin, Dalia; Filleur, Stéphanie; Bhowmick, Reshma; Henkin, Jack; Miller, Stephen D.; Ifergan, Igal; Lee, Yesung; Osman, Iman; Thaxton, C. Shad; Volpert, Olga V.

doi:10.1038/s41467-017-01433-3

Cited by 238 publications

(201 citation statements)

References 67 publications

(90 reference statements)

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“…The phenotypes of the EVs were analyzed by flow cytometry. [28] As shown in Figure 2F,G, trypsin/proteinase K digestion eliminated most of the EVs transmembrane protein CD63 but not CD40L, suggesting that CD40L is contained within EVs. Similar to their parent CD4 + T cells, CD4 + T cell EVs expressed CD4 + T cell-related molecules on their surfaces, such as CD4, CD25, and ICOS, but we did not observe the expression of CD40L compared to the expression of isotype control ( Figure 2D), which was consistent with a previous study.…”

Section: Characterization Of Evs From Activated Cd4 + T Cellsmentioning

confidence: 84%

CD4⁺ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

Lü

Xie

et al. 2019

Advanced Science

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T cells secrete bioactive extracellular vesicles (EVs), but the potential biological effects of CD4+ T cell EVs are not clear. The main purpose of this study is to investigate the effects of CD4+ T cell–derived EVs on B cell responses and examine their role in antigen‐mediated humoral immune responses. In this study, CD4+ T cell EVs are purified from activated CD4+ T cells in vitro. After immunization with the Hepatitis B surface antigen (HBsAg) vaccine, CD4+ T cell EVs‐treated mice show stronger humoral immune responses, which is indicated by a greater Hepatitis B surface antibody (HBsAb) level in serum and a greater proportion of plasma cells in bone marrow. In addition, it is found that EVs released from activated CD4+ T cells play an important role in B cell responses in vitro, which significantly promote B cell activation, proliferation, and antibody production. Interestingly, antigen‐specific CD4+ T cell EVs are found to be more efficient than control EVs in enhancing B cell responses. Furthermore, it is shown that CD40 ligand (CD40L) is involved in CD4+ T cell EVs‐mediated B cell responses. Overall, the results have demonstrated that CD4+ T cell EVs enhance B cell responses and serve as a novel immunomodulator to promote antigen‐specific humoral immune responses.

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Section: Characterization Of Evs From Activated Cd4 + T Cellsmentioning

confidence: 84%

CD4⁺ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

Lü

Xie

et al. 2019

Advanced Science

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“…In the context of cancer, nonclassical monocytes migrate toward metastatic sites within the lung, where they engulf tumor material and generate cytokines that regulate antitumor immunity . Tumor‐derived exosomes also expand bone marrow pools of patrolling monocytes, which appears to initiate an immune surveillance cascade that prevents metastatic seeding …”

Section: Functions In Cancermentioning

confidence: 99%

Monocyte heterogeneity and functions in cancer

Olingy

Dinh

Hedrick

2019

Journal of Leukocyte Biology

362

310

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Monocytes are innate immune cells of the mononuclear phagocyte system that have emerged as important regulators of cancer development and progression. Our understanding of monocytes has advanced from viewing these cells as a homogenous population to a heterogeneous system of cells that display diverse responses to different stimuli. During cancer, different monocyte subsets perform functions that contribute to both pro‐ and antitumoral immunity, including phagocytosis, secretion of tumoricidal mediators, promotion of angiogenesis, remodeling of the extracellular matrix, recruitment of lymphocytes, and differentiation into tumor‐associated macrophages and dendritic cells. The ability of cancer to evade immune recognition and clearance requires protumoral signals to outweigh ongoing attempts by the host immune system to prevent tumor growth. This review discusses current understanding of monocyte heterogeneity during homeostasis, highlights monocyte functions in cancer progression, and describes monocyte‐targeted therapeutic strategies for cancer treatment.

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“…Exosomes from premetastatic melanoma cells were suggested to inhibit metastasis, by instigating immune-surveillance programs at the metastatic site. 46 Conversely, melanoma-secreted exosomes were recently shown to contain PD-L1, that contributed to systemic immunosuppression in patients and with response to immunotherapy. 47 Thus, signaling by tumor-derived exosomes may be context dependent, and caution should be taken when designing exosome-targeted therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

Melanoma‐derived extracellular vesicles instigate proinflammatory signaling in the metastatic microenvironment

Lahav

Adler

Zait

et al. 2019

Intl Journal of Cancer

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The major cause of melanoma mortality is metastasis to distant organs, including lungs and brain. Reciprocal interactions of metastasizing tumor cells with stromal cells in secondary sites play a critical role in all stages of tumorigenesis and metastasis. Changes in the metastatic microenvironment were shown to precede clinically relevant metastases, and may occur prior to the arrival of disseminated tumor cells to the distant organ, thus creating a hospitable “premetastatic niche.” Exosomes secreted by tumor cells were demonstrated to play an important role in the preparation of a hospitable metastatic niche. However, the functional role of melanoma‐derived exosomes on metastatic niche formation, and the downstream pathways activated in stromal cells at the metastatic niche are largely unresolved. Here we show that extracellular vesicles (EVs) secreted by metastatic melanoma cells that spontaneously metastasize to lungs and to brain, activate proinflammatory signaling in lung fibroblasts and in astrocytes. Interestingly, unlike paracrine signaling by melanoma cells, EVs secreted by metastatic melanoma cells instigated a proinflammatory gene signature in lung fibroblasts but did not activate wound‐healing functions, suggesting that tumor cell‐secreted EVs activate distinct CAF characteristics and tumor‐promoting functions. Moreover, melanoma‐secreted EVs also activated proinflammatory signaling in astrocytes, indicating that EV‐mediated reprogramming of stromal cells is a general mechanism of modulating the metastatic niche in multiple distant organs. Thus, our study demonstrates that melanoma‐derived EVs reprogram tumor‐promoting functions in stromal cells in a distinct manner, implicating a central role for tumor‐derived EV signaling in promoting the formation of an inflammatory metastatic niche.

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Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche

Cited by 238 publications

References 67 publications

CD4⁺ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

CD4⁺ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

Monocyte heterogeneity and functions in cancer

Melanoma‐derived extracellular vesicles instigate proinflammatory signaling in the metastatic microenvironment

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Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche

Cited by 238 publications

References 67 publications

CD4+ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

CD4+ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

Monocyte heterogeneity and functions in cancer

Melanoma‐derived extracellular vesicles instigate proinflammatory signaling in the metastatic microenvironment

Contact Info

Product

Resources

About

CD4⁺ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

CD4⁺ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses