Inflammatory regulatory T cells in the microenvironments of ulcerative colitis and colon carcinoma

Kryczek, Ilona; Wang, Lin; Wu, Ke; Li, Wei; Zhao, Ende; Cui, Tracy X.; Wei, Shuang; Liu, Yan; Wang, Yin; Vatan, Linda; Szeliga, Wojciech; Greenson, Joel K.; Roliński, Jacek; Zgodziński, Witold; Huang, Emina; Tao, Kaixiong; Wang, Guobin; Zou, Weiping

doi:10.1080/2162402x.2015.1105430

Cited by 33 publications

(29 citation statements)

References 47 publications

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“…The genes that encode T H 1-type chemokines are repressed by epigenetic mechanisms in cancer, and this affects the numbers of antitumour effector immune cells that are present within tumours, determines the cancer immune phenotype, and shapes the therapeutic efficacy of immune checkpoint blockade, adoptive T cell therapy and conventional therapy 10,172,173 . By contrast, the chemokines associated with the tumour trafficking of myeloid cells, T reg cells and T H 22 cells can directly and indirectly influence the biological phenotype of a tumour (for example, whether it is a stem/EMT-type or non-stem/EMT-type tumour) 30,34,43,73,86 . Thus, direct and indirect manipulation of chemokine–chemokine receptor signalling pathways may reshape the immune and biological phenotypes of a tumour in a manner that increases the therapeutic efficacy of immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…T reg cells may express inflammatory cytokines — including CXCL8 (also known as IL-8) 43 and IL-17 (REF. 44) — in the human colon cancer microenvironment.…”

Section: Immune Cell Tumour Traffickingmentioning

confidence: 99%

“…Tumour cells and myeloid cells express CXCL8, and recruit neutrophils into the tumour microenvironment 91 . Certain subsets of T reg cells in the human cancer microenvironment express CXCL8 and promote neutrophil migration into tumours 43 . Neutrophils secrete various molecules that support and promote tumour angiogenesis.…”

Section: Chemokines and Tumour-associated Apcsmentioning

confidence: 99%

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Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy

2017

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The tumour microenvironment is the primary location in which tumour cells and the host immune system interact. Different immune cell subsets are recruited into the tumour microenvironment via interactions between chemokines and chemokine receptors, and these populations have distinct effects on tumour progression and therapeutic outcomes. In this Review, we focus on the main chemokines that are found in the human tumour microenvironment; we elaborate on their patterns of expression, their regulation and their roles in immune cell recruitment and in cancer and stromal cell biology, and we consider how they affect cancer immunity and tumorigenesis. We also discuss the potential of targeting chemokine networks, in combination with other immunotherapies, for the treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

“…T reg cells may express inflammatory cytokines — including CXCL8 (also known as IL-8) 43 and IL-17 (REF. 44) — in the human colon cancer microenvironment.…”

Section: Immune Cell Tumour Traffickingmentioning

confidence: 99%

Section: Chemokines and Tumour-associated Apcsmentioning

confidence: 99%

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Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy

2017

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“…Their release by tumor cells can be impaired by PGE2 or increased by administration of L. monocytogenes-based anticancer vaccines (Bronger et al 2012;Guirnalda et al 2013). CXCL8 is produced by tumor cells and subsets of T reg cells in the human cancer microenvironment, which promotes neutrophil migration into tumors (Kryczek et al 2016;Waugh and Wilson 2008). Moreover, CXCL8 is targeting vascular endothelial cells and tumor cells and thus supports angiogenesis, tumor progression, and metastasis (De Larco et al 2004;Lee et al 2012, Nagarsheth et al 2017.…”

Section: Role Of Chemokines In Tumor Immunology and In Immunotherapymentioning

confidence: 99%

Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

Merle

Fischbacher

Liepert

et al. 2019

Immunological Investigations

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In cancer or hematologic disorders, chemokines act as growth-or survival factors, regulating hematopoiesis and angiogenesis, determining metastatic spread and controlling leukocyte infiltration into tumors to inhibit antitumor immune responses. The aim was to quantify the release of CXCL8, −9, −10, CCL2, −5, and IL-12 in AML/ MDS-pts' serum by cytometric bead array and to correlate data with clinical subtypes and courses. Minimal differences in serum-levels subdivided into various groups (e.g. age groups, FAB-types, blastproportions, cytogenetic-risk-groups) were seen, but higher release of CXCL8, −9, −10 and lower release of CCL2 and −5 tendentially correlated with more favorable subtypes (<50 years of age, <80% blasts in PB). Comparing different stages of the disease higher CCL5-release in persisting disease and a significantly higher CCL2release at relapse were found compared to first diagnosispointing to a change of 'disease activity' on a chemokine level. Correlations with later on achieved response to immunotherapy and occurrence of GVHD were seen: Higher values of CXCL8, −9, −10 and CCL2 and lower CCL5-values correlated with achieved response to immunotherapy. Predictive cut-off-values were evaluated separating the groups in 'responders' and 'non-responders'. Higher levels of CCL2 and −5 but lower levels of CXCL8, −9, −10 correlated with occurrence of GVHD. We conclude, that in AML-pts' serum higher values of CXCL8, −9, −10 and lower values of CCL5 and in part of CCL2 correlate with more favorable subtypes and improved antitumor'-reactive function. This knowledge can contribute to develop immune-modifying strategies that promote antileukemic adaptive immune responses.

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“…T cell proliferation and the production of cytokines which initiate effector functions were inhibited by this subset whilst IL-8 induced inflammatory cytokine release and neutrophil infiltration was also recorded. The researchers labelled the cells as an inflammatory Treg subgroup which could initiate tumour development in an inflammatory setting such as the development of CRC from chronic UC [65].…”

Section: The Effect Of Regulatory Treg Cellsmentioning

confidence: 99%

CCR6-CCL20 Axis in IBD: What have we learnt in the past 20 years?

Ranasinghe¹,

Eri²

2018

Preprint

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Inflammatory bowel disease (IBD) is a CC chemokine receptor 6 (CCR6) -associated immune mediated disorder which has attracted an extensive superfluity of experimental analyses. IBD has come to the fore of varied scrutinizing owing to its complexity by nature for comprising of two synergistic sub phenotypes; Crohn's disease (CD) and Ulcerative colitis (UC). Both these disease entities cause potent immune dysregulation followed by intense tissue damage within the gut mucosal system, initiating symptoms which are severely debilitating. Multiple causative factors are said to be responsible for IBD but direct immune dysfunction is kindled by overplay of innate and adaptive immune responses produced against a pathogenic microbial attack through the weakened or leaky gut epithelial barrier. Once immune homeostasis is not achieved by tolerating agents, the self-assertive adaptive immunity mobilize its various T and B cell cohorts initializing their allied immune mechanisms by vigorously deploying them towards the site of infection. CCR6 and its unique solitary ligand CC-chemokine ligand 20 (CCL20) are small protein molecules which are abundantly expressed by T and B lymphocytes and act as chemotactic immune-modulatory envoys that help in the deployment of the effector lymphocyte arm of the immune system, producing two directly opposing outcomes in IBD. This dichotomous immunity consists of either immune tolerance or inflammation which then develops into a chronic state, remaining catatonic to inherent immunity or targeted clinical therapy. In this review, we have chronologically identified a plethora of experimental studies radiating into 14 different compartments highlighted in the visual depiction which have employed both mouse models and clinical subjects spanning a period of nearly two decades. In doing so, we expect the research community would further benefit by tracing through the history, thereby understanding the CCR6 -CCL20 axis in IBD and identifying the gaps in literature which can be fortuitously filled in the future.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:

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Inflammatory regulatory T cells in the microenvironments of ulcerative colitis and colon carcinoma

Abstract: Foxp3C

Cited by 33 publications

References 47 publications

Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy

Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy

Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

CCR6-CCL20 Axis in IBD: What have we learnt in the past 20 years?

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