Peptide vaccination induces profound changes in the immune system in patients with B-cell chronic lymphocytic leukemia

Giannopoulos, Krzysztof; Własiuk, Paulina; Dmoszyńska, Anna; Roliński, Jacek; Schmitt, Michael

doi:10.5603/fhc.2011.0023

Cited by 10 publications

(7 citation statements)

References 28 publications

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“…In contrast to solid tumors, little is known about the immunobiology of Th17 cells in hematologic malignancies, particularly CLL [90]. Initial studies about the IL-17 producing T cells in CLL were recently performed in a limited sample size and showed highly variable results [91][92][93]. Following these observations, we showed that the frequencies of both Th17 and Tc17 cells were markedly decreased in CLL patients and correlated with disease progression.…”

Section: Th17 Cells In Cllmentioning

confidence: 79%

“…The frequency of Th17 cells was about 3% of the total CD4 + T cells in a limited number of CLL/SLL patients [91] The highly variable number of IL-17 producing CD4 + and CD8 + T cells [92,93] Decreased frequencies of both Th17 and Tc17 cells which was correlated with disease progression [94] Increased frequency of IL-17 producing follicular Th cells which was correlated with advanced CLL stages [95] Treatment of CLL patients with lenalidomide led to induction of Th17 cells [93] Increased frequency of IL-17 producing T cells in CLL/SLL patients compared with other B cell malignancies [91] Increased frequency of Th17 cells was correlated with better prognostic markers and longer survival The microenvironmental milieu in leukemic spleens enhances the recruitment and expansion of Th17 and other IL-17-expressing cells [97] Decreased Th17 and IL-17A levels which were correlated with progressive disease IL-17A inversely correlated with the time from CLL diagnosis to the start of therapy [98] CLL/SLL: Chronic lymphocytic leukemia/small lymphocytic lymphoma; IL: Interleukin; Th: T helper. [94].…”

Section: Main Claimmentioning

confidence: 99%

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The Skewed Balance Between Tregs and Th17 in Chronic Lymphocytic Leukemia

et al. 2015

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While Tregs maintain self-tolerance and inhibit antitumor responses, T helper (Th)17 cells may enhance inflammatory and antitumor responses. The balance between these two important T-cell subsets has been skewed in many immunopathologic conditions such as autoimmune and cancer diseases. B-cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western world and is characterized with monoclonal expansion of B lymphocytes. There is evidence which implies that the progression of CLL is associated with expansion of Treg and downregulation of Th17 cells. In this review, we will discuss about immunobiology of Treg and Th17 cells and their role in immunopathogenesis of CLL as well as their reciprocal changes during disease progression.

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Section: Th17 Cells In Cllmentioning

confidence: 79%

Section: Main Claimmentioning

confidence: 99%

The Skewed Balance Between Tregs and Th17 in Chronic Lymphocytic Leukemia

et al. 2015

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“…Indeed, spectrometric studies on the naturally presented HLA ligands in CLL identified a pool of antigens exclusively expressed in CLL patients, providing information regarding the immunogenicity of the malignant cells while also offering new treatment targets ( 107 ). However, clinical studies targeting neoepitopes expressed in the malignant cells demonstrate enhanced rejection of tumor cells, underling the safety profile of these approaches ( 124 , 125 ).…”

Section: Treatment Options In Cll and Implication Of The T Cell Compamentioning

confidence: 99%

T Cells in Chronic Lymphocytic Leukemia: A Two-Edged Sword

2021

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Chronic lymphocytic leukemia (CLL) is a malignancy of mature, antigen-experienced B lymphocytes. Despite great progress recently achieved in the management of CLL, the disease remains incurable, underscoring the need for further investigation into the underlying pathophysiology. Microenvironmental crosstalk has an established role in CLL pathogenesis and progression. Indeed, the malignant CLL cells are strongly dependent on interactions with other immune and non-immune cell populations that shape a highly orchestrated network, the tumor microenvironment (TME). The composition of the TME, as well as the bidirectional interactions between the malignant clone and the microenvironmental elements have been linked to disease heterogeneity. Mounting evidence implicates T cells present in the TME in the natural history of the CLL as well as in the establishment of certain CLL hallmarks e.g. tumor evasion and immune suppression. CLL is characterized by restrictions in the T cell receptor gene repertoire, T cell oligoclonal expansions, as well as shared T cell receptor clonotypes amongst patients, strongly alluding to selection by restricted antigenic elements of as yet undisclosed identity. Further, the T cells in CLL exhibit a distinctive phenotype with features of “exhaustion” likely as a result of chronic antigenic stimulation. This might be relevant to the fact that, despite increased numbers of oligoclonal T cells in the periphery, these cells are incapable of mounting effective anti-tumor immune responses, a feature perhaps also linked with the elevated numbers of T regulatory subpopulations. Alterations of T cell gene expression profile are associated with defects in both the cytoskeleton and immune synapse formation, and are generally induced by direct contact with the malignant clone. That said, these abnormalities appear to be reversible, which is why therapies targeting the T cell compartment represent a reasonable therapeutic option in CLL. Indeed, novel strategies, including CAR T cell immunotherapy, immune checkpoint blockade and immunomodulation, have come to the spotlight in an attempt to restore the functionality of T cells and enhance targeted cytotoxic activity against the malignant clone.

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“…The vaccine had similar immunological (i.e., increase in R3-specific CD8+ cells) and clinical response in patients with chronic lymphocytic leukemia (Giannopoulos et al, 2010). Interestingly, although patients with CML are characterized as having immunosuppression, the vaccine caused profound changes (mostly an increase) in different T cell subsets and in cytokines that are involved in immune response (i.e., TGF-β, IL-10, IL-2, and TNF) during the vaccination period (Giannopoulos, Wlasiuk, Dmoszynska, Rolinski, & Schmitt, 2011). However, despite the early success with the R3-peptide vaccine, it was recently shown that only baseline RHAMM expression was present in both leukemic stem cells (CD34+CD38−) and hematopoietic stem cells (CD34+CD38−) from healthy control cells.…”

Section: Targeting Ha Receptorsmentioning

confidence: 99%

Targeting Hyaluronic Acid Family for Cancer Chemoprevention and Therapy

Lokeshwar

Mirza

Jordan

2014

Advances in Cancer Research

138

113

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Hyaluronic acid or hyaluronan (HA) is perhaps one of the most uncomplicated large polymers that regulates several normal physiological processes and, at the same time, contributes to the manifestation of a variety of chronic and acute diseases, including cancer. Members of the HA signaling pathway (HA synthases, HA receptors, and HYAL-1 hyaluronidase) have been experimentally shown to promote tumor growth, metastasis, and angiogenesis, and hence each of them is a potential target for cancer therapy. Furthermore, as these members are also overexpressed in a variety of carcinomas, targeting of the HA family is clinically relevant. A variety of targeted approaches have been developed to target various HA family members, including small-molecule inhibitors and antibody and vaccine therapies. These treatment approaches inhibit HA-mediated intracellular signaling that promotes tumor cell proliferation, motility, and invasion, as well as induction of endothelial cell functions. Being nontoxic, nonimmunogenic, and versatile for modifications, HA has been used in nanoparticle preparations for the targeted delivery of chemotherapy drugs and other anticancer compounds to tumor cells through interaction with cell-surface HA receptors. This review discusses basic and clinical translational aspects of targeting each HA family member and respective treatment approaches that have been described in the literature.

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Peptide vaccination induces profound changes in the immune system in patients with B-cell chronic lymphocytic leukemia

Cited by 10 publications

References 28 publications

The Skewed Balance Between Tregs and Th17 in Chronic Lymphocytic Leukemia

The Skewed Balance Between Tregs and Th17 in Chronic Lymphocytic Leukemia

T Cells in Chronic Lymphocytic Leukemia: A Two-Edged Sword

Targeting Hyaluronic Acid Family for Cancer Chemoprevention and Therapy

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