Th22 cells increase in poor prognosis multiple myeloma and promote tumor cell growth and survival

Lullo, Giulia Di; Marcatti, Magda; Heltai, Silvia; Brunetto, Emanuela; Tresoldi, Cristina; Bondanza, Attilio; Bonini, Chiara; Ponzoni, Maurilio; Tonon, Giovanni; Ciceri, Fabio; Bordignon, Claudio; Protti, Maria Pia

doi:10.1080/2162402x.2015.1005460

Cited by 39 publications

(44 citation statements)

References 55 publications

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“…Importantly, the percentage of Th22 cells in ISS stage III MM patients is significantly higher compared with patients with ISS stage I/II, demonstrating that in MM increased frequency of Th22 cells associates with poor prognosis. 6 In support of our findings, increased IL-22 serum levels were also recently detected in MM patients with active disease. 29 Mechanistically, we demonstrated how the Th22 prototypical cytokines IL-22 and IL-13 exert both direct and indirect tumor-promoting functions in MM.…”

Section: Th22 Cells In MMsupporting

confidence: 78%

“…6 We found that Th22 (i.e., IL-22 C IL-17 ¡ IL-13 C ) cells are significantly increased in peripheral blood (PB) and BM of ISS stage III and relapsed/refractory MM patients compared with healthy donors and patients with asymptomatic (i.e., MGUS and SMM) or ISS stage I/II disease. Importantly, the percentage of Th22 cells in ISS stage III MM patients is significantly higher compared with patients with ISS stage I/II, demonstrating that in MM increased frequency of Th22 cells associates with poor prognosis.…”

Section: Th22 Cells In MMmentioning

confidence: 88%

“…To confirm the distinctive roles of Th22 and Th17 cells in MM, we took advantage of our previously described cohort of MM patients 6 and compared the frequency of the two Th cell subsets in relation to the clinical status and the presence of bone lesions.…”

Section: Th17 and Th22 Cells Within The Same Cohort Of MM Patientsmentioning

confidence: 99%

“…29 Mechanistically, we demonstrated how the Th22 prototypical cytokines IL-22 and IL-13 exert both direct and indirect tumor-promoting functions in MM. 6 IL-22 directly increases tumor cell growth and resistance to drug-induced cell death on MM plasma cells by binding to its receptor IL22RA1, which is aberrantly expressed in a fraction of primary tumors. IL-13 augments adhesive molecule expression and IL-6 secretion by BM-MSCs, which are responsive to IL-13 as other cells of stromal/fibroblastic origin, 30 indirectly fostering MM cell proliferation.…”

Section: Th22 Cells In MMmentioning

confidence: 99%

“…4 Th1 cells promote tumor rejection through secretion of interferon (IFN)-g, Th2 cells primarily favor tumor progression through secretion of interleukin (IL)-4, IL-5 and IL-13, while the role Th17 cells that secrete IL-17 and IL-22 is more debated and appears to be tumor-dependent. 4 More recently, an additional Th cell subset (i.e., Th22 cells), whose characteristics are discussed below, has been studied in several tumor models, 5 among which MM, 6 collectively suggesting a correlation with poor prognosis and tumor-promoting functions.…”

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Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

2015

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Section: Th22 Cells In MMsupporting

confidence: 78%

Section: Th22 Cells In MMmentioning

confidence: 88%

Section: Th17 and Th22 Cells Within The Same Cohort Of MM Patientsmentioning

confidence: 99%

Section: Th22 Cells In MMmentioning

confidence: 99%

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confidence: 99%

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Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

2015

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High MutS homolog 2 expression predicts poor prognosis and is related to immune infiltration in endometrial carcinoma

Ying

Zhang

et al. 2022

Cell Biology International

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Several studies have shown that MutS homolog 2 (MSH2) is highly expressed in many cancer tissues. Transcriptome expression data were collected from the Cancer Genome Atlas (TCGA) database. We analyzed the expression of MSH2 in normal and tumor tissues, the relationship between MSH2 expression and various prognostic factors, and the relationship between MSH2 expression and overall survival, disease specific survival, and progression free interval. We also examined MSH2 promoter methylation between endometrial cancer and normal endometrial tissues, and identified the prognostic value of MSH2 methylation in endometrial cancer. MSH2 was highly expressed in endometrial cancer tumor tissues compared with normal tissues. High MSH2 expression might be an independent prognostic factor for OS, DSS, and PFI. Further, high MSH2 expression was correlated with age and histological type, but not with BMI, clinical stage, tumor invasion, or other clinical features. MSH2 promoter methylation in endometrial cancer was significantly lower than in normal tissues. Additionally, MSH2 levels, OS, DSS, and PFI were associated with BMI, age, tumor invasion, and histological type. ssGSEA showed that MSH2 expression was positively correlated with the infiltration of Th2 cells, Tcm cells, T helper cells, and Tgd cells, whereas it was negatively correlated with NK CD56 bright cells, pDC cells, iDC cells, cytotoxic cells, and neutrophils. Increased MSH2 expression and reduced MSH2 methylation in endometrial cancer predicts poor prognosis. MSH2 may be used as a biomarker for the diagnosis and prognosis of endometrial cancer and as an immunotherapy target.

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A catch‐22: Interleukin‐22 and cancer

2018

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Barrier surfaces of multicellular organisms are in constant contact with the environment and infractions to the integrity of epithelial surfaces is likely a frequent event. Interestingly, components of the immune system, that can be activated by environmental compounds such as the microbiota or nutrients, are interspersed among epithelial cells or directly underlie the epithelium. It is now appreciated that immune cells continuously receive and integrate signals from the environment. Curiously, such continuous reception of stimulation does not normally trigger an inflammatory response but mediators produced by immune cells in response to such signals seem to rather promote barrier integrity and repair. The molecular mediators involved in this process are poorly understood. In recent years, the cytokine interleukin-22, produced mainly by group 3 innate lymphoid cells (ILCs), has been studied as a paradigm for how immune cells can control various aspects of epithelial cell function because expression of its receptor is restricted to non-hematopoietic cells. We will summarize here the diverse roles of IL-22 for the malignant transformation of epithelial cells, for tumor growth, wound healing and tissue repair. Furthermore, we will discuss IL-22 as a potential therapeutic target. Keywords:Aryl hydrocarbon receptor r Cancer r IL-22 r Innate lymphoid cells r RORγt IntroductionBarrier organs like the skin, the gut and lung mucosae are in constant contact with the environment. Their cellular components need to adapt to the continuous and ever changing presence of a large number of microbes (i.e., bacteria, fungi, viruses and parasites collectively referred to as the "microbiome") and their metabolites, including toxins. In addition, the epithelial barrier of the intestine is also subjected to food components, some of which are toxic by being poisonous, noxious or irritating. The skin barrier is exposed to UV irradiation, which is beneficial (e.g., conversion of Vitamin D) but can also be harmful (e.g., direct and Correspondence: Dr. Andreas Diefenbach e-mail: andreas.diefenbach@charite.de indirect DNA damage). Thus, barrier surfaces with the environment are sites where adaptive processes are initiated. Over millions of years of co-evolution of multicellular organisms with their habitat, adaptive signaling networks have been selected that are believed to shield the organism against such continuous threats and, thereby, shape their fitness. A well-studied example of such adaptive processes is microbiota-host relationships [1]. Through contact with microbial communities, epithelial function is being modified as to minimize damage to the barrier. For example, epithelial cells directly receive signals from the microbiota leading to the production of anti-bacterial proteins and to the protection of epithelial cells against TNF-triggered apoptosis [2][3][4]. * These authors contributed equally to this work.C 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 16Pedro Hernandez et al. Eur. J. Immunol. 2018. 48: ...

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Th22 cells increase in poor prognosis multiple myeloma and promote tumor cell growth and survival

Cited by 39 publications

References 55 publications

Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

High MutS homolog 2 expression predicts poor prognosis and is related to immune infiltration in endometrial carcinoma

A catch‐22: Interleukin‐22 and cancer

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