IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis

Coffelt, Seth B.; Kersten, Kelly; Doornebal, Chris W.; Weiden, Jorieke; Vrijland, Kim; Hau, Cheei-Sing; Verstegen, Niels J M; Ciampricotti, Metamia; Hawinkels, Lukas J.A.C.; Jonkers, Jos; Visser, Karin E. de

doi:10.1038/nature14282

Cited by 1,367 publications

(1,462 citation statements)

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“…Pro‐tumour function of γδ 17 cells has been demonstrated in several cancer models, including a breast cancer metastasis model72 and an ovarian cancer model,73 and the roles of γδ 17 cells in the development of tumours have been reviewed elsewhere 74. Abundant γδ 17 cell infiltration accompanied by immunosuppressive myeloid‐derived suppressor cells is found in human colorectal cancer with positive correlation with advanced tumour clinicopathological features, suggesting that γδ 17 cells induce myeloid‐derived suppressor cell‐mediated immunosuppression 75.…”

Section: γδ17 Cells In Tumoursmentioning

confidence: 99%

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Akitsu

Iwakura

2018

Immunology

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SummaryInterleukin‐17 (IL‐17) is a pro‐inflammatory cytokine and is involved in the development of many diseases. Recent studies have revealed that IL‐17‐producing γδ T cells (γδ17 cells) in addition to IL‐17‐producing CD4+ T cells [T helper type 17 (Th17) cells] are often the main producers of IL‐17 in mouse models of inflammatory diseases. γδ T cells are functionally committed during intra‐thymic differentiation. γδ thymocytes capable of producing IL‐17, which express the transcription factor retinoic‐acid‐receptor‐related orphan receptor γt and the signature cytokine receptor IL‐23R, leave the thymus, and produce IL‐17 rapidly by the stimulation with IL‐1β and IL‐23 in the periphery. Therefore, γδ17 cells play important roles in the early phase of host defence against pathogens and in inflammatory diseases. γδ T cells that can produce IL‐17 are also increased in the skin of patients with psoriasis and in peripheral blood of patients with ankylosing sclerosis. Indeed, the therapy targeting IL‐17 has been approved or is in clinical trials, and proved to be very efficient to treat psoriasis, psoriatic arthritis and ankylosing sclerosis. In this review, we discuss recent knowledge about the pathophysiological function of γδ17 cells in infection and inflammatory diseases and therapeutic advances targeting IL‐17.

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Section: γδ17 Cells In Tumoursmentioning

confidence: 99%

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Akitsu

Iwakura

2018

Immunology

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“…Clinical support for a role of neutrophils in chemotherapy response comes from observations in a variety of cancer patients, such as breast and non-small cell lung cancer patients, where chemotherapyinduced neutropenia is associated with better patient prognosis [46,47]. We and others have established a metastasis-promoting role for neutrophils in breast and melanoma models [48][49][50]. Therefore, targeting neutrophils or their mediators may synergize with chemotherapeutics to specifically decrease metastasis.…”

Section: Innate Immune Cellsmentioning

confidence: 97%

“…Interestingly, CD4 + T cells appear to be the source of IL17 in these tumor models and IL17 regulates G-CSF expression in tumor-associated fibroblasts. We have recently shown that IL17-producing γδ T cells induce systemic expression of G-CSF to expand immunosuppressive neutrophils and facilitate breast cancer metastasis [49]. In this regard, targeting the IL17-producing T cell-G-CSFneutrophil axis in combination with anti-angiogenic therapies may benefit patients with metastatic disease.…”

Section: Immune Cell Function Following Vascular-targeting Agentsmentioning

confidence: 99%

“…Their role in tumorigenesis is rather paradoxical [201]. Whereas CD8 + T cells potentially recognize and kill tumor cells, CD4 + T cells, Tregs, B cells and γδ T cells play a more sinister role in tumor biology [49,64,65,78,202]. In tumor-bearing hosts, crosstalk between adaptive and innate immune cells fosters disease progression.…”

Section: Box 2: Immune Complexity In Tumor-bearing Hostsmentioning

confidence: 99%

“…In tumor-bearing hosts, crosstalk between adaptive and innate immune cells fosters disease progression. Tumor-associated myeloid cells frequently suppress CD8 + T cells and induce Tregs, while at the same time, cells of the adaptive immune system, notably B lymphocytes, CD4 + T cells and γδ T cells, can actually contribute to the expansion and pro-tumor polarization of myeloid cells in tumor bearing hosts [49,64,65,78,202].…”

Section: Box 2: Immune Complexity In Tumor-bearing Hostsmentioning

confidence: 99%

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Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Coffelt

Visser

2015

Trends in Immunology

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125

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SummaryConventional anti-cancer therapies, such as chemotherapy, radiotherapy and targeted therapy, are designed to kill cancer cells. Yet, the efficacy of anti-cancer therapies is not only determined by their direct effects on cancer cells, but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit a number of changes in immune-related parameters including the composition, phenotype and function of immune cells. In this review, we discuss the impact of innate and adaptive immune cells on the success of anti-cancer therapy, we examine the opportunities to exploit host immune responses to boost tumor clearing and we highlight the challenges facing the treatment of advanced metastatic disease. Then and now: The link between the immune system and anti-cancer therapiesThe relationship between anti-cancer therapies and the immune system is as old as the invention of anti-cancer therapies themselves. After the use of mustard gas in the trenches of World War I, a seminal observation was made that some exposed soldiers displayed severe loss of bone marrow and lymph node cells [1]. This observation then spurred the idea that the anti-proliferative capacity of mustard gas may also slow the growth of cancer cells.Experiments carried out in mice transplanted with lymphoid tumors were convincing enough to treat a lymphoma patient [2], and these events initiated the standardized treatment of cancer patients with chemotherapy [3,4].Fast forward 100 years later. The influence of immune cells on tumor progression and metastasis is well established [5], and an appreciation for the immune system's impact during conventional anti-cancer therapy treatment is growing. Recent seminal advances indicate that immune cells can shape the outcome of various anti-cancer therapies. As such, 2 immune cells and their molecular mediators have evolved into bona vide targets of therapeutic manipulation in cancer patients. The recent breakthrough of immunotherapeutics that inhibit negative immune regulatory pathways, such as anti-CTLA4 and anti-PD1, has initiated a new era in the treatment of cancer [6]. In parallel, immunomodulatory strategies aimed at dampening pro-tumor functions of immune cells are currently being tested in cancer patients [7]. Immune cells also function as reliable biomarkers, since their abundance or activation status often predicts how well patients respond to a particular treatment regimen.Here, we review these novel experimental and clinical insights, highlighting potential implications for the development of synergistic therapies designed to combat primary tumors and, more importantly, metastatic disease. The pros and cons of experimental mouse modelsResearch questions aimed at understanding the role of immune cells during anti-cancer therapy require models that mirror the complex interactions between the immune system and diverse forms of human cancers. Transplantable cancer cell line models and carcinogeninduced cancer models are the most frequently used for these purposes. However...

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Epidermal activation of Hedgehog signaling establishes an immunosuppressive microenvironment in basal cell carcinoma by modulating skin immunity

et al. 2020

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Activation of hedgehog/glioma‐associated oncogene homolog (HH/GLI) signaling induces basal cell carcinoma (BCC) and establishes an immunosuppressive tumor microenvironment. HH/GLI signaling inhibits the activity of antitumoral T cells via programmed death ligand 1/programmed death‐1 immune checkpoint signaling and the recruitment of immunosuppressive regulatory T cells. BCCs also show strong infiltration with antitumoral neutrophils. The data support the evaluation of combination treatments with HH inhibitors and immune checkpoint blockers.

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IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis

Cited by 1,367 publications

References 34 publications

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Epidermal activation of Hedgehog signaling establishes an immunosuppressive microenvironment in basal cell carcinoma by modulating skin immunity

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