Oxidative stress in CLL patients leads to activation of Th9 cells: an experimental and comprehensive survey

Sabry, Sabry A.; El-Senduny, Fardous F.; Abousamra, Nashwa K.; El-Din, Manal Salah; Youssef, Magdy M.

doi:10.1080/25785826.2019.1700747

Cited by 6 publications

(10 citation statements)

References 36 publications

(42 reference statements)

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“…We and others recently reported the overexpression of IL-9 in leukemic cells from CLL patients [ 14 , 15 , 90 , 91 , 92 ] and Eμ-TCL1 mice [ 15 ], a well-established CLL mouse model [ 93 ]. Interestingly, this enhanced expression correlates with hallmarks of aggressive disease, such as unmutated Immunoglobulin Heavy Variable (IgHV) genes, ectopic expression of ζ-associated protein of 70 kDa (ZAP-70), and high levels of the surface glycoprotein CD38 [ 14 , 15 , 90 ].…”

Section: Il-9 Acts As a Pro-tumoral Soluble Factor In Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 99%

“…Moreover, it correlates with lower overall survival of CLL patients [ 15 ]. IL-9 is also overexpressed in sera and peripheral blood from CLL patients [ 92 ], mainly as a result of uncontrolled secretion by Th9 cells [ 91 ].…”

Section: Il-9 Acts As a Pro-tumoral Soluble Factor In Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 99%

“…A recent report by Sabry and colleagues showed that high levels of circulating IL-9 and Th9 cells strongly correlate with oxidative stress in leukemic cells from CLL patients, which, in turn, correlates with markers of unfavorable prognosis, such as abnormal immunophenotype and cytogenetic aberrations. These results strongly suggest the existence of a link between Th9-secreted IL-9 and oxidant-dependent injury in CLL B cells, although the underlying molecular mechanism remains to be clarified [ 91 ].…”

Section: Il-9 Acts As a Pro-tumoral Soluble Factor In Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 99%

“…These findings indicate that, in the specific context of CLL, IL-9 is overexpressed not only by Th9 cells, but also by leukemic cells themselves. Irrespective of the cells involved in the secretion of this cytokine, the increased amount of IL-9 in the CLL tumor microenvironment has been proven to promote tumor development [ 14 , 15 , 90 , 91 ]. To date, the effects of this cytokine on the immune components of the tumor microenvironment have not been investigated.…”

Section: Il-9 Acts As a Pro-tumoral Soluble Factor In Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 99%

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Interleukin (IL)-9 Supports the Tumor-Promoting Environment of Chronic Lymphocytic Leukemia

Patrussi

Capitani

Baldari

2021

Cancers

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Interleukin (IL)-9 is a soluble factor secreted by immune cells into the microenvironment. Originally identified as a mediator of allergic responses, IL-9 has been detected in recent years in several tumor niches. In solid tumors, it mainly promotes anti-tumor immune responses, while in hematologic malignancies, it sustains the growth and survival of neoplastic cells. IL-9 has been recently implicated in the pathogenesis of chronic lymphocytic leukemia; however, the molecular mechanisms underlying its contribution to this complex neoplasia are still unclear. Here, we summarize the current knowledge of IL-9 in the tumor microenvironment, with a focus on its role in the pathogenesis of chronic lymphocytic leukemia.

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Section: Il-9 Acts As a Pro-tumoral Soluble Factor In Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 99%

Section: Il-9 Acts As a Pro-tumoral Soluble Factor In Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 99%

Section: Il-9 Acts As a Pro-tumoral Soluble Factor In Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 99%

Section: Il-9 Acts As a Pro-tumoral Soluble Factor In Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 99%

See 2 more Smart Citations

Interleukin (IL)-9 Supports the Tumor-Promoting Environment of Chronic Lymphocytic Leukemia

Patrussi

Capitani

Baldari

2021

Cancers

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“…In CLL patients it is associated with reduced number of memory T cells and a shift toward Th9 cells. The Th9 cells are a subpopulation of CD4 + T cells, characterized by the secretion of IL-9, the cytokine linked with leukemogenesis ( 82 ). Tregs are another CD4 + T cell subpopulation which is enriched in B-cell malignancies ( 83 , 84 ).…”

Section: How Oxidative Stress Affects Immune Response?mentioning

confidence: 99%

cROSsing the Line: Between Beneficial and Harmful Effects of Reactive Oxygen Species in B-Cell Malignancies

2020

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B-cell malignancies are a heterogeneous group of hematological neoplasms derived from cells at different stages of B-cell development. Recent studies revealed that dysregulated redox metabolism is one of the factors contributing to the pathogenesis and progression of B-cell malignancies. Elevated levels of oxidative stress markers usually correlate with the advanced stage of various B-cell malignancies. In the complex tumor microenvironment, reactive oxygen species affect not only malignant cells but also bystander cells, including immune cells. Importantly, malignant cells, due to genetic dysregulation, are able to adapt to the increased demands for energy and reducing equivalents via metabolic reprogramming and upregulation of antioxidants. The immune cells, however, are more sensitive to oxidative imbalance. This may cause their dysfunction, leading to immune evasion and tumor progression. On the other hand, the already imbalanced redox homeostasis renders malignant B-cells particularly sensitive to further elevation of reactive oxygen species. Indeed, targeting antioxidant systems has already presented anti-leukemic efficacy in preclinical models. Moreover, the prooxidant treatment that triggers immunogenic cell death has been utilized to generate autologous anti-leukemic vaccines. In this article, we review novel research on the dual role of the reactive oxygen species in B-cell malignancies. We highlight the mechanisms of maintaining redox homeostasis by malignant B-cells along with the antioxidant shield provided by the microenvironment. We summarize current findings regarding therapeutic targeting of redox metabolism in B-cell malignancies. We also discuss how the oxidative stress affects antitumor immune response and how excessive reactive oxygens species influence anticancer prooxidant treatments and immunotherapies.

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T cells in health and disease

Sun,

Su,

Jiao

et al. 2023

Sig Transduct Target Ther

158

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T cells are crucial for immune functions to maintain health and prevent disease. T cell development occurs in a stepwise process in the thymus and mainly generates CD4+ and CD8+ T cell subsets. Upon antigen stimulation, naïve T cells differentiate into CD4+ helper and CD8+ cytotoxic effector and memory cells, mediating direct killing, diverse immune regulatory function, and long-term protection. In response to acute and chronic infections and tumors, T cells adopt distinct differentiation trajectories and develop into a range of heterogeneous populations with various phenotype, differentiation potential, and functionality under precise and elaborate regulations of transcriptional and epigenetic programs. Abnormal T-cell immunity can initiate and promote the pathogenesis of autoimmune diseases. In this review, we summarize the current understanding of T cell development, CD4+ and CD8+ T cell classification, and differentiation in physiological settings. We further elaborate the heterogeneity, differentiation, functionality, and regulation network of CD4+ and CD8+ T cells in infectious disease, chronic infection and tumor, and autoimmune disease, highlighting the exhausted CD8+ T cell differentiation trajectory, CD4+ T cell helper function, T cell contributions to immunotherapy and autoimmune pathogenesis. We also discuss the development and function of γδ T cells in tissue surveillance, infection, and tumor immunity. Finally, we summarized current T-cell-based immunotherapies in both cancer and autoimmune diseases, with an emphasis on their clinical applications. A better understanding of T cell immunity provides insight into developing novel prophylactic and therapeutic strategies in human diseases.

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Oxidative stress in CLL patients leads to activation of Th9 cells: an experimental and comprehensive survey

Cited by 6 publications

References 36 publications

Interleukin (IL)-9 Supports the Tumor-Promoting Environment of Chronic Lymphocytic Leukemia

Interleukin (IL)-9 Supports the Tumor-Promoting Environment of Chronic Lymphocytic Leukemia

cROSsing the Line: Between Beneficial and Harmful Effects of Reactive Oxygen Species in B-Cell Malignancies

T cells in health and disease

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