Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in response to TLR9 and CD40 activation

In conclusion, CLL cells demonstrate a unique clonal quality of adopting Breg properties which promote modulation of T-cell characteristics. TLR9 appears to be a potent activator of regulatory abilities in CLL cells, possibly contributing to preferential immune escape of TLR9-responsive cells.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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ConclusionsSamalizumab had a good safety profile and treatment was associated with reduced tumor burden in a majority of patients with advanced CLL. These preliminary positive results support further development of samalizumab as an immune checkpoint inhibitor.Trial registrationClinicalTrials.gov,NCT00648739 registered April 1, 2008.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
AbstractExperience in the use of CAR T cells to treat CLL is limited, but safety and efficacy data are encouraging, suggesting that it may be possible to use CAR T cells in populations of CLL patients with particularly unfavorable prognoses. Mechanisms intrinsic to the pathophysiology of CLL undoubtedly explain the efficacy reported based on limited data for the first few series, and underlie the rationale of successive modulations in lymphodepletion schemes, transgene constructs, and, finally, the therapeutic association of CAR T cells with ibrutinib, which appears to be particularly promising. This review describes the p...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
In this report, we present a case of pembrolizumab-induced autoimmune hemolytic anemia and pancytopenia in a patient who was receiving pembrolizumab treatment for metastatic melanoma. This patient has a history of chronic lymphocytic leukemia and was diagnosed with metastatic melanoma in 2017. He developed symptomatic AIHA and pancytopenia after receiving 8 cycles of pembrolizumab in 2018. Pembrolizumab treatment was discontinued and he was treated with blood transfusion and prednisone. After 5 months of tapering prednisone treatment, his anemia and pancytopenia have improved toward successful recovery. Cancer patients alr...
Source: Case Reports in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions The clinical trials discussed here, which include several trials investigating novel therapeutic targets, demonstrate that translational research in pemphigus and pemphigoid is a fast-growing field. We thus expect that several novel treatments will be shortly available for the treatment of pemphigus and pemphigoid patients. Given the high, and thus far unmet, medical need in this field (110), this is highly encouraging and will hopefully improve the quality of life of the affected patients. In addition to the compounds and targets described here, several new targets have been recently identified in preclinical...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Tabea Haug1, Michael Aigner1, Moritz M. Peuser1, Carolin D. Strobl1, Kai Hildner2, Dimitrios Mougiakakos1, Heiko Bruns1, Andreas Mackensen1 and Simon Völkl1* 1Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany 2Department of Internal Medicine 1, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany The recently discovered population of TCRαβ+ CD4–/CD8– (double-negative, DN) T-cells are highly potent suppressor cells in mice and humans. In preclinical transplantation m...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsThese data establish the critical role of a newly discovered BCR independent Ca2+ entry in CLL evolution, provide new insights into CLL pathophysiology, and support innovative therapeutic perspectives such as targeting STIM1 located at the plasma membrane.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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