Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer

Hagerling, Catharina; González, Hugo; Salari, Kiarash; Wang, Chih‐Yang; Lin, Charlene; Robles, Isabella; Gogh, Merel van; Dejmek, Annika; Jirström, Karin; Werb, Zena

doi:10.1073/pnas.1907660116

Cited by 70 publications

(55 citation statements)

References 53 publications

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“…In apparent contrast with the previous findings, neutrophils recruitment and activation in the metastatic niche was found to be important for the reduction of metastasis formation through the killing of cancer cells [ 162 , 163 ]. Genetic ablation of the atypical chemokine receptor 2 (ACKR2) resulted in increased levels of chemokine receptors (i.e.…”

Section: The Role Of Neutrophils In Cancercontrasting

confidence: 82%

“…A recent study has demonstrated a mechanism that may explain, at least in part, why breast cancer patients develop metastasis [ 162 ]. The injection of human breast cancer cells with low spontaneous metastatic potential in non-obese diabetic (NOD)/severe combined immunodeficient (SCID) mice, resulted in reprogramming of neutrophils in the pre-metastatic lung.…”

Section: The Role Of Neutrophils In Cancermentioning

confidence: 99%

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The complexity of neutrophils in health and disease: Focus on cancer

Carnevale

Ghasemi

Rigatelli

et al. 2020

Seminars in Immunology

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Neutrophils are essential soldiers of the immune response and their role have long been restricted to their activities in defence against microbial infections and during the acute phase of the inflammatory response. However, increasing number of investigations showed that neutrophils are endowed with plasticity and can participate in the orchestration of both innate and adaptive immune responses. Neutrophils have an impact on a broad range of disorders, including infections, chronic inflammations, and cancer. Neutrophils are present in the tumour microenvironment and have been reported to mediate both pro-tumour and anti-tumour responses. Neutrophils can contribute to genetic instability, tumour cell proliferation, angiogenesis and suppression of the anti-tumour immune response. In contrast, neutrophils are reported to mediate anti-tumour resistance by direct killing of tumour cells or by engaging cooperative interactions with other immune cells. Here we discuss the current understandings of neutrophils biology and functions in health and diseases, with a specific focus on their role in cancer biology and their prognostic significance in human cancer.

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Section: The Role Of Neutrophils In Cancercontrasting

confidence: 82%

Section: The Role Of Neutrophils In Cancermentioning

confidence: 99%

The complexity of neutrophils in health and disease: Focus on cancer

Carnevale

Ghasemi

Rigatelli

et al. 2020

Seminars in Immunology

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“…Non-metastatic cancer cells can mobilize IFNγ-producing monocytes to the lungs. IFNγ release activates TMEM173/STING within neutrophils, which stimulates neutrophil-mediated killing of disseminated cancer cells in the lungs ( 24 ).…”

Section: Anti-tumor Neutrophil Functionsmentioning

confidence: 99%

Neutrophils: Orchestrators of the Malignant Phenotype

2020

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Neutrophils are the first leukocytes recruited to sites of inflammation, where they execute anti-microbial functions to eliminate infectious agents. These functions include phagocytosis, release of reactive oxygen species and the formation of neutrophil extracellular traps via NETosis. Neutrophils are receiving increasing attention in the context of cancer, where these same neutrophil-associated functions are also important for modulating tumor growth and metastatic progression. Neutrophils are phenotypically heterogeneous and, depending on the context, exert anti-or pro-tumorigenic functions. Increasing evidence also suggests an important role of neutrophils and their involvement in promoting multiple steps of the metastatic cascade. The steps include: (1) local invasion and intravasation of cancer cells into circulation, (2) survival of cancer cells in the bloodstream and extravasation at a distant site, (3) early cancer cell seeding/survival, and (4) progressive growth of cancer cells to form macroscopic metastases. Although neutrophil functions designed to eliminate infectious agents can also eliminate tumor cells, their dysregulation can promote tumor growth and enable metastasis at multiple steps along the metastatic cascade. In this review, we will provide an overview of the current advances in neutrophil biology in the context of cancer. We also discuss the emerging field of immunometabolism, in which the rewiring of alternative metabolic pathways within neutrophils can impact their pro-tumorigenic/pro-metastatic functions.

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“…In addition, the microenvironment in the (pre)metastatic organ may induce dormancy 11 by different signals such as an endothelial cell-derived thrombospondin-1 12 or TGF-β2 produced in the bone marrow 13 . Only few studies addressed the influence of cancer cell-extrinsic factors such as innate 14,15 and adaptive immunity 16,17 on dormancy. Although infiltration of the primary tumor by T cells was shown to correlate with a good prognosis 18 , it 5 remains unclear whether this correlation is explained by cytotoxic T cells that eliminate cancer cells or by T cells that prevent the outgrowth of cancer cells and induce dormancy 19,20 .…”

Section: Introductionmentioning

confidence: 99%

CD39⁺PD-1⁺CD8⁺T cells mediate metastatic dormancy in breast cancer

Lara

Castañón

Vermeer

et al. 2020

Preprint

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Some breast tumors metastasize aggressively whereas others remain in a state of metastatic dormancy for months or even years. The mechanism governing such metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping, we identified a discrete population of CD39 + PD-1 + CD8 + T cells present both in primary tumors and in dormant metastasis, which was hardly found in aggressively metastasizing tumors. Of note, the adoptive transfer of purified CD39 + PD-1 + CD8 + T cells prevented metastatic outgrowth.In human breast cancer, the frequency of CD39 + PD-1 + CD8 + but not of total CD8 + T cells correlated with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39 + PD-1 + CD8 + T cells for controlling experimental and human breast cancer.Furthermore, density of CD39 + PD-1 + CD8 + T cells may serve as a novel biomarker and may serve as a potential immunotherapy target. Here, we discovered that a primary breast tumor primes a systemic, CD39 + PD-1 + CD8 + T cell response that is essential for metastatic dormancy in the lungs.3

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Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer

Cited by 70 publications

References 53 publications

The complexity of neutrophils in health and disease: Focus on cancer

The complexity of neutrophils in health and disease: Focus on cancer

Neutrophils: Orchestrators of the Malignant Phenotype

CD39⁺PD-1⁺CD8⁺T cells mediate metastatic dormancy in breast cancer

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Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer

Cited by 70 publications

References 53 publications

The complexity of neutrophils in health and disease: Focus on cancer

The complexity of neutrophils in health and disease: Focus on cancer

Neutrophils: Orchestrators of the Malignant Phenotype

CD39+PD-1+CD8+T cells mediate metastatic dormancy in breast cancer

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Product

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CD39⁺PD-1⁺CD8⁺T cells mediate metastatic dormancy in breast cancer