The Role of Neutrophils in the Pathogenesis of Chronic Lymphocytic Leukemia

Wachowska, Malgorzata; Wojciechowska, Alicja; Muchowicz, Angelika

doi:10.3390/ijms23010365

Cited by 13 publications

(10 citation statements)

References 82 publications

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“…In addition, neutrophils infiltrated in the leukemic niche were observed to secrete survival cytokines, including APRIL and BAFF, which are important for B cell proliferation. Finally, the neutrophil depletion in Eμ-TCL1 mice, with already developed CLL, demonstrated a reduction in the leukemic burden in spleens, clearly showing that neutrophils support leukemia progression in Eμ-TCL1 mice ( 65 , 66 ).…”

Section: Tumor-associated Neutrophils (Tans)mentioning

confidence: 84%

“…Indeed, stromal cells from the leukemic microenvironment have been shown to interact substantially with neutrophils ( 65 , 66 ). A study realized in an Eμ-TCL1 CLL murine model indicated that stromal cells from red pulp and the marginal zone of spleens presented LCs infiltrate, overexpressed genes related to neutrophil chemotaxis, including the chemotactic factors S100A8 and S100A9 (MRP8 and MRP14, respectively), the chemokine receptor CXCR2, the pro-inflammatory cytokine IL-1β, and integrin CD11b (Itgam) ( 65 , 66 ). In addition, neutrophils infiltrated in the leukemic niche were observed to secrete survival cytokines, including APRIL and BAFF, which are important for B cell proliferation.…”

Section: Tumor-associated Neutrophils (Tans)mentioning

confidence: 99%

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The Yin-Yang of myeloid cells in the leukemic microenvironment: Immunological role and clinical implications

et al. 2022

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The leukemic microenvironment has a high diversity of immune cells that are phenotypically and functionally distinct. However, our understanding of the biology, immunology, and clinical implications underlying these cells remains poorly investigated. Among the resident immune cells that can infiltrate the leukemic microenvironment are myeloid cells, which correspond to a heterogeneous cell group of the innate immune system. They encompass populations of neutrophils, macrophages, and myeloid-derived suppressor cells (MDSCs). These cells can be abundant in different tissues and, in the leukemic microenvironment, are associated with the clinical outcome of the patient, acting dichotomously to contribute to leukemic progression or stimulate antitumor immune responses. In this review, we detail the current evidence and the many mechanisms that indicate that the activation of different myeloid cell populations may contribute to immunosuppression, survival, or metastatic dissemination, as well as in immunosurveillance and stimulation of specific cytotoxic responses. Furthermore, we broadly discuss the interactions of tumor-associated neutrophils and macrophages (TANs and TAMs, respectively) and MDSCs in the leukemic microenvironment. Finally, we provide new perspectives on the potential of myeloid cell subpopulations as predictive biomarkers of therapeutical response, as well as potential targets in the chemoimmunotherapy of leukemias due to their dual Yin-Yang roles in leukemia.

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Section: Tumor-associated Neutrophils (Tans)mentioning

confidence: 84%

Section: Tumor-associated Neutrophils (Tans)mentioning

confidence: 99%

The Yin-Yang of myeloid cells in the leukemic microenvironment: Immunological role and clinical implications

et al. 2022

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“…Although our data confirm that phagocytes including resident monocytes support T-ALL progression, targeting these cells did not improve mice survival. We also independently studied neutrophils, a key cell population in inflammation, and showed that these cells are not implicated in T-ALL progression, albeit participating in other hematological malignancies like Chronic Lymphocytic Leukemia 54 or B lymphomas 55 . Studying the role of neutrophils and resident monocytes in T-ALL was also motivated by their crucial and complex role in infections 56 or in cancers 57 and since they are the most increased cell populations in the periphery of our leukemic mice.…”

Section: Discussionmentioning

confidence: 99%

T-cell acute lymphoblastic leukemia progression is supported by inflammatory molecules including Hepatocyte Growth factor

Le Maout,

Fahy,

Renou

et al. 2024

Preprint

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Background: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disorder characterized by an increased proliferation of immature T lymphocytes precursors. T-ALL treatment includes chemotherapy with strong side effects, and patients that undergo relapse display poor prognosis. Although cell-intrinsic oncogenic pathways are well-studied, the tumor microenvironment, like inflammatory cellular and molecular components is less explored in T-ALL. We sought to determine the composition of the inflammatory microenvironment induced by T-ALL, and its role in T-ALL progression. Methods: Two mouse T-ALL cell models were injected into immunocompetent mice. We used anti-Ly6G, and clodronate liposomes to suppress neutrophils and phagocytes, respectively. 5-(N-ethylcarboxamido)adenosine (NECA), an agonist of adenosine receptors was used to decrease inflammatory molecules secretion. Findings: We show that T-ALLs enhance blood neutrophils and resident monocytes, accompanied with a plasmatic acute secretion of inflammatory molecules. Depleting neutrophils or resident monocytes does not modulate plasmatic inflammatory molecule secretion and mice survival. However, inhibiting the secretion of inflammatory molecules by microenvironment with NECA diminishes T-ALL progression enhancing mouse survival. We uncovered Hepatocyte Growth Factor (HGF), T-ALL-driven and the most decreased molecule with NECA, as a potential therapeutic target in T-ALL. Interpretation: Altogether, we identified a signature of inflammatory molecules that can potentially be involved in T-ALL evolution and uncovered HGF as a new potential therapeutic target.

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“…Нейтрофилы реагируют на различные медиаторы, высвобождаемые в микроокружении опухоли, что приводит к активации их либо противоопухолевых, либо проопухолевых фенотипов. Данная нейтрофильная пластичность обусловлена влиянием трансформирующего фактора роста β (TGFß), β-интерфероном (ИФН-β), ИЛ-35, а также концентрацией цитокинов и кислорода в микроокружении опухоли [4].…”

Section: роль нейтрофилов в развитии ракаunclassified

“…Противоопухолевая активность нейтрофилов N1 связана с прямым уничтожением опухолевых клеток путем выработки активных форм кислорода (АФК) и оксида азота или индукцией апоптоза, связанного с активацией Fas/TRAIL. Другие механизмы включают антителозависимую клеточно-опосредованную цитотоксичность (ADCC) и активацию функции Т-клеток [8].…”

Section: роль нейтрофилов в развитии ракаunclassified

Neutrophils as Factors That Can Stimulate and Prevent the Development of Cancer. The Role of Neutrophils in Metastasis, Prognosis and Possible Points for Therapeutic Interventions

Golubtsova¹,

Kantysheva²,

Novoselova³

et al. 2022

НО МН (SR MS)

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В данном обзоре приводится накопленная актуальная информация о роли нейтрофилов в патогенезе онкологических заболеваний. Показано, что нейтрофилы вносят неоднозначный, однако значительный вклад в развитие опухолевого процесса: с одной стороны, они способствуют росту опухоли, ее метастазированию и инвазии, а также поддерживают опухолевый ангиогенез, содействуя распространению заболевания, но, с другой стороны, нейтрофилы сдерживают и ограничивают рост опухоли за счет экспрессируемых факторов некроза опухоли, активных форм кислорода и индукции различных хемокинов и цитокинов. Данная противоречивость в эффектах нейтрофилов создает проблемы в оценке их истинной роли в онкогенезе. Нейтрофильные внеклеточные ловушки, обнаруживаемые в слюне, сыворотке крови и опухолевой ткани, и отношение нейтрофилов к лимфоцитам в крови может указывать на степень злокачественности опухоли и иметь большое прогностическое значение. На сегодняшний день нейтрофилы, а также воздействие на их метаболические пути являются перспективным направлением в иммунотерапии рака: например воздействие на нейтрофил-опосредованный ангиогенез может достоверно подавлять рост опухолей, снижать гипоксию ткани и уменьшать инфильтрацию нейтрофилов.

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The Role of Neutrophils in the Pathogenesis of Chronic Lymphocytic Leukemia

Cited by 13 publications

References 82 publications

The Yin-Yang of myeloid cells in the leukemic microenvironment: Immunological role and clinical implications

The Yin-Yang of myeloid cells in the leukemic microenvironment: Immunological role and clinical implications

T-cell acute lymphoblastic leukemia progression is supported by inflammatory molecules including Hepatocyte Growth factor

Neutrophils as Factors That Can Stimulate and Prevent the Development of Cancer. The Role of Neutrophils in Metastasis, Prognosis and Possible Points for Therapeutic Interventions

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