Increased Frequency of CD8<sup>+</sup>and CD4<sup>+</sup>Regulatory T Cells in Chronic Lymphocytic Leukemia: Association with Disease Progression

Jadidi‐Niaragh, Farhad; Yousefi, Mehdi; Memarian, Ali; Hojjat‐Farsangi, Mohammad; Khoshnoodi, Jalal; Razavi, Seyed Mohsen; Jeddi-Tehrani, Mahmood; Shokri, Fazel

doi:10.3109/07357907.2012.756110

Cited by 51 publications

(44 citation statements)

References 48 publications

(86 reference statements)

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“…The purity of isolated cells was more than 95%, as investigated by flow cytometry. Transfection of T cells with PD‐1 siRNA‐loaded NPs to suppress the expression of PD‐1 was performed according to our previous report …”

Section: Methodsmentioning

confidence: 99%

“…Briefly, 400 ll CDS NPs loaded with 10 lg siRNA molecules were mixed with 200 ll fetal bovine serum and gently shaken at 37°. Twenty-microliter samples were then collected at predetermined times (2,6,12,18,24, and 36 hr), and stored at À20°for subsequent analysis by gel electrophoresis.…”

Section: Validation and Characterization Of The Cds Npsmentioning

confidence: 99%

“…CD3 + T cells were purified from the spleen and tumor samples using a T-cell isolation kit (Miltenyi Biotec, Bergisch Gladbach, Germany), through a negative selection method as described previously. 24 The purity of isolated cells was more than 95%, as investigated by flow cytometry. Transfection of T cells with PD-1 siRNAloaded NPs to suppress the expression of PD-1 was performed according to our previous report.…”

Section: Isolation Of T Cells By Macs Cell Separation and Transfectiomentioning

confidence: 99%

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Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

et al. 2019

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Summary Dendritic cell (DC) ‐based cancer immunotherapy is one of the most important anti‐cancer immunotherapies, and has been associated with variable efficiencies in different cancer types. It is well‐known that tumor microenvironment plays a key role in the efficacy of various immunotherapies such as DC vaccine. Accordingly, the expression of programmed death ligand 1 (PD‐L1) on DCs, which interacts with PD‐1 on T cells, leads to inhibition of anti‐tumor responses following presentation of tumor antigens by DCs to T cells. Therefore, we hypothesized that down‐regulation of PD‐L1 in DCs in association with silencing of PD‐1 on T cells may lead to the enhancement of T‐cell priming by DCs to have efficient anti‐tumor T‐cell responses. In this study, we silenced the expression of PD‐L1 in DCs and programmed cell death protein 1 (PD‐1) in T cells by small interfering RNA (siRNA) ‐loaded chitosan–dextran sulfate nanoparticles (NPs) and evaluated the DC phenotypic and functional characteristics and T‐cell functions following tumor antigen recognition on DCs, ex vivo. Our results showed that synthesized NPs had good physicochemical characteristics (size 77·5 nm and zeta potential of 14·3) that were associated with efficient cellular uptake and target gene silencing. Moreover, PD‐L1 silencing was associated with stimulatory characteristics of DCs. On the other hand, presentation of tumor antigens by PD‐L1‐negative DCs to PD‐1‐silenced T cells led to induction of potent T‐cell responses. Our findings imply that PD‐L1‐silenced DCs can be considered as a potent immunotherapeutic approach in combination with PD‐1‐siRNA loaded NPs, however; further in vivo investigation is required in animal models.

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Section: Methodsmentioning

confidence: 99%

Section: Validation and Characterization Of The Cds Npsmentioning

confidence: 99%

Section: Isolation Of T Cells By Macs Cell Separation and Transfectiomentioning

confidence: 99%

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Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

et al. 2019

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“…There are studies suggesting that chemokines such as CCL3 and CCL4, secreted by the very B-CLL clone, are capable to recruit T regs, in order to ensure a proximate source of survival signals [40]. The precise role played by T regs in B-CLL is not fully elucidated, but recent studies prove that CD4+ T regs have the capacity to inhibit policlonal B cells and effector T cells, downregulating the anti-tumoral response in B-CLL [41]. CD8+ T cells are found to be increased in our patient group whenever the clinical manifestations are present.…”

Section: Discussionmentioning

confidence: 99%

Specific Associations Between Clinical Signs, Immune Cells, Disease Genetic Background and Burden in a Group of Patients with B-Cell Chronic Lymphocytic Leukemia

Grigore¹,

Ivanov²,

Zlei³

et al. 2014

Romanian Review of Laboratory Medicine

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Traffic of tumor-and normal cells through the peripheral blood (PB) of patients with B-cell chronic lymphocytic leukemia (B-CLL) to the lymph nodes (LN) or spleen/ liver sites is governed by specific changes in CCR7, CXCR5, CXCR3, CCR4, CD3, CD4, CD8, CD27, CD28, CD45RA, CD25, CD127, CD38 was also report a significant increase in the frequency of total T cells and T cell subsets (effector-and central memory CD4+ T cells, regulatory T cells, follicular T helper cells, distinct functional CD8+ T cells) with the occurrence of specific clinical manifestations. Chemokine receptor expression on circulating CD4+ T cell subsets was augmented in connection to

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“…Lack of response in this small analysis can be attributed to suboptimal dosing and duration of therapy. Additionally, CD4+ and CD8+ regulatory T cells are positively correlated with disease progression in CLL and likely function to suppress T cell expansion induced by blinatumomab, thereby constituting a potential mechanism of resistance to therapy [45]. We are unaware of any currently available blinatumomab trials enrolling patients with CLL or MZL.…”

Section: Pharmacology Pharmacokinetics and Immunologic Response mentioning

confidence: 99%

Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies

Rogala

Freyer

Ontiveros

et al. 2015

Expert Opinion on Biological Therapy

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Introduction The approval of blinatumomab signals the long awaited arrival of immunotherapy for acute lymphoblastic leukemia (ALL). Previous options for relapsed or refractory disease were restricted to combination cytotoxic chemotherapy with limited efficacy and significant toxicity. Through an innovative mechanism of action, blinatumomab stimulates a polyclonal antitumor T cell response, yielding unprecedented single agent efficacy in the relapsed/refractory setting. Success comes at the cost of immunological toxicities rarely encountered with previous therapies and challenging administration logistics requiring clinical expertise. Areas covered All published clinical and preclinical studies using blinatumomab were reviewed in addition to all registered ongoing clinical trials and data published in abstract form. The search was limited to the English language. The pharmacology, clinical efficacy, toxicity profile, and logistical considerations for drug administration are discussed. Expert Opinion Blinatumomab is an exciting addition to the treatment armamentarium for relapsed/refractory ALL, yet several questions remain regarding optimal implementation into the current treatment paradigm. A unique toxicity profile should be weighed against promising benefits in a poor prognosis population. Other emerging therapies, such as chimeric antigen receptor-modified T cells and inotuzumab ozogamicin, with different side effect profiles and administration schedules, may prove to be more beneficial for specific patient populations.

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Increased Frequency of CD8⁺and CD4⁺Regulatory T Cells in Chronic Lymphocytic Leukemia: Association with Disease Progression

Cited by 51 publications

References 48 publications

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

Specific Associations Between Clinical Signs, Immune Cells, Disease Genetic Background and Burden in a Group of Patients with B-Cell Chronic Lymphocytic Leukemia

Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies

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Increased Frequency of CD8+and CD4+Regulatory T Cells in Chronic Lymphocytic Leukemia: Association with Disease Progression

Cited by 51 publications

References 48 publications

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

Specific Associations Between Clinical Signs, Immune Cells, Disease Genetic Background and Burden in a Group of Patients with B-Cell Chronic Lymphocytic Leukemia

Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies

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Increased Frequency of CD8⁺and CD4⁺Regulatory T Cells in Chronic Lymphocytic Leukemia: Association with Disease Progression