Patrolling monocytes control tumor metastasis to the lung

Hanna, Richard N.; Cekic, Caglar; Sağ, Duygu; Tacke, Robert; Thomas, Graham D.; Nowyhed, Heba; Herrley, Erica; Rasquinha, Nicole; McArdle, Sara; Wu, Runpei; Peluso, Esther; Metzger, Daniel; Ichinose, Hiroshi; Shaked, Iftach; Chodaczek, Grzegorz; Biswas, Subhra K.; Hedrick, Catherine C.

doi:10.1126/science.aac9407

Cited by 399 publications

(408 citation statements)

References 45 publications

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“…The lung is maintained by suction with a force great enough to lessen the physiological motion into a level compatible with high-resolution dynamic microscopic imaging [18,24,28,29,[43][44][45][46][47][48][49][50]. In particular, the resolution reached using this technique recently permitted observation of dendritic cell dendrites (Figure 2d) [44] and patrolling monocytes controlling tumor metastasis to the lung [51].…”

Section: Suctionmentioning

confidence: 99%

Intravital microscopy of the lung: minimizing invasiveness

Fiole

Tournier

2016

Journal of Biophotonics

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In vivo microscopy has recently become a gold standard in lung immunology studies involving small animals, largely benefiting from the democratization of multiphoton microscopy allowing for deep tissue imaging. This technology represents currently our only way of exploring the lungs and inferring what happens in human respiratory medicine. The interest of lung in vivo microscopy essentially relies upon its relevance as a study model, fulfilling physiological requirements in comparison with in vitro and ex vivo experiments. However, strategies developed in order to overcome movements of the thorax caused by breathing and heartbeats remain the chief drawback of the technique and a major source of invasiveness. In this context, minimizing invasiveness is an unavoidable prerequisite for any improvement of lung in vivo microscopy. This review puts into perspective the main techniques enabling lung in vivo microscopy, providing pros and cons regarding invasiveness.

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Section: Suctionmentioning

confidence: 99%

Intravital microscopy of the lung: minimizing invasiveness

Fiole

Tournier

2016

Journal of Biophotonics

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“…In breast cancer models, classical monocytes are recruited to metastatic sites and promote extravasation and subsequent growth of cancer cells (8). In contrast, it was reported that patrolling monocytes prevent melanoma metastasis to the lung by recruiting NK cells (9). The prevailing view is that metastasis occurs as a late event in cancer progression (10).…”

Section: Introductionmentioning

confidence: 99%

Primary Tumors Limit Metastasis Formation through Induction of IL15-Mediated Cross-Talk between Patrolling Monocytes and NK Cells

Kubo

Mensurado

Gonçalves-Sousa

et al. 2017

Cancer Immunology Research

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Metastases are responsible for the vast majority of cancerrelated deaths. Although tumor cells can become invasive early during cancer progression, metastases formation typically occurs as a late event. How the immune response to primary tumors may dictate this outcome remains poorly understood, which hampers our capacity to manipulate it therapeutically. Here, we used a twostep experimental model, based on the highly aggressive B16F10 melanoma, that temporally segregates the establishment of primary tumors (subcutaneously) and the formation of lung metastases (from intravenous injection). This allowed us to identify a protective innate immune response induced by primary tumors that inhibits experimental metastasis. We found that in the presence of primary tumors, increased numbers of natural killer (NK) cells with enhanced IFNg, granzyme B, and perforin production were recruited to the lung upon metastasis induction. These changes were mirrored by a local accumulation of patrolling monocytes and macrophages with high expression of MHC class II and NOS2. Critically, the protective effect on metastasis was lost upon patrolling monocyte or NK cell depletion, IL15 neutralization, or IFNg ablation. The combined analysis of these approaches allowed us to establish a hierarchy in which patrolling monocytes, making IL15 in response to primary tumors, activate NK cells and IFNg production that then inhibit lung metastasis formation. This work identifies an innate cell network and the molecular determinants responsible for "metastasis immunosurveillance," providing support for using the key molecular mediator, IL15, to improve immunotherapeutic outcomes.

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“…PMo depend on the transcription factor N4a1 for their development from bone marrow precursors [4] and in pathological conditions they can respond to a variety of stimuli, contributing to resolution of inflammation [5]. In a recent study by Hanna et al [6], a new anti-tumoral function of PMo has been demonstrated in different models of murine metastasis. This function of mouse surveillance resulted in increased killing of metastatic cells by natural killer (NK) cells.…”

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confidence: 99%

“…In conclusion, the study by Hanna et al [6] by the tumor via a CCL2-mediated mechanism; they extravasate into the lung tissue where they differentiate into MAMs and interact with cancer cells, promoting their extravasation and the formation of micrometastasis. These recruited IMo differentiate into MAMs and secrete CCL3 that enhances their retention in the tissue.…”

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confidence: 99%

Cancer immunosurveillance: role of patrolling monocytes

Cassetta

Pollard

2015

Cell Res

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npg Classical inflammatory monocytes and their derivative macrophages promote tumor metastasis whereas CD8 + T and NK cells restrict tumor growth. In a recent paper published in Science, Hanna and colleagues demonstrate that another monocyte population, nonclassical patrolling monocytes, is enriched in the microvasculature of tumor-challenged lung and reduces tumor metastasis by recruiting NK cells.Tumor metastasis accounts for 95% of cancer-related deaths in the developed world. In the past decade focus has shifted from study of cancer cells alone to the tumor microenvironment that consists of many cell types that overall support cancer progression. Circulating monocytes extravasate into the tissue and differentiate into macrophages, which are key players in the regulation of metastasis as they provide support for the extravasation, survival and growth of metastatic cancer cells [1].There are at least two circulating monocyte populations in the blood: classical "inflammatory" monocytes (IMo, CCR2 High Ly6C + in mouse; CCR2 High CD14 ++ CD16 -in human) and nonclassical "patrolling" monocytes (PMo, CX3CR1 High Ly6C -in mouse; CX3CR1 High CD14 + CD16 + in human). IMo are recruited to inflammatory sites through the CCR2-CCL2 axis; they extravasate, differentiate into tissue macrophages and dendritic cells, and respond to bacterial and parasitic infections. In breast cancer models, IMo are also recruited via the CCL2-CCR2 axis to metastatic sites where they promote cancer cell extravasation and survival [2].

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Patrolling monocytes control tumor metastasis to the lung

Cited by 399 publications

References 45 publications

Intravital microscopy of the lung: minimizing invasiveness

Intravital microscopy of the lung: minimizing invasiveness

Primary Tumors Limit Metastasis Formation through Induction of IL15-Mediated Cross-Talk between Patrolling Monocytes and NK Cells

Cancer immunosurveillance: role of patrolling monocytes

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