The role of T-cells in the pathogenesis of chronic lymphocytic leukemia has recently gained much attention due to the importance of the constant interaction between neoplastic B-cells with microenvironment substratum and T-cells. It is believed that these interactions modulate the clinical course of the disease, mainly through the regulation of the expansion, differentiation, and survival of chronic lymphocytic leukemia B-cells. Importantly, this crosstalk may also change the number, function, and memory phenotype of normal T-cells, thereby altering the amplitude and/or efficiency of adaptive immunity in chronic lymphocytic leukemia patients. The present study presents an overview on important aspects of this immunological crosstalk, particularly on the abnormalities of chronic lymphocytic leukemia B-cells and the alterations in normal T-cells, with focus on the CD4 memory T-cell compartment that could offer survival signals to chronic lymphocytic leukemia B-cell clone(s) and contribute to the establishment and progression of the disease. The authors believe that understanding the biological consequences of the interaction between normal T- and neoplastic B-cells in chronic lymphocytic leukemia may allow for improvements in the prognostic information and therapeutic approaches for this disease.© 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. All rights reserved.
BackgroundAlthough chronic lymphocytic leukemia is basically a B cell disease, its pathophysiology and evolution are thought to be significantly influenced by T cells, as these are probably the most important interaction partner of neoplastic B cells, participating in their expansion, differentiation and survival. Chronic lymphocytic leukemia B cells may also drive functional and phenotypic changes of non-malignant T cells. There are few data about the association between memory T cells and prognosis, especially related to ZAP-70, a common reliable surrogate of the gold standard chronic lymphocytic leukemia prognostic markers.ObjectiveThe aim of this study was to investigate whether the expression of ZAP-70 in chronic lymphocytic leukemia patients is associated with abnormal patterns of the distribution of naïve and memory T cells related to crosstalk between these cells.MethodsIn this cross-sectional, controlled study, patients with chronic lymphocytic leukemia were compared with healthy blood donors regarding the expression of ZAP-70 and the distribution of naïve and memory T cell subsets in peripheral blood as measured by flow cytometry.ResultsZAP-70 positive patients presented an increased frequency and absolute number of central memory CD4+ T cells, but not CD8+ T cells, compared to ZAP-70 negative patients and age-matched apparently healthy donors.ConclusionsBecause central memory CD4+ T cells are located in lymph nodes and express CD40L, we consider that malignant ZAP-70-positive B cells may receive beneficial signals from central memory CD4+ T cells as they accumulate, which could contribute to more aggressive disease.
Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of epithelial keratinocytes that represents a growing public health problem. It is one of the most common solid cancers worldwide with rate of 9.2/100,000 people. In 2016, the estimate in Brazil is 6.3/100,000 men and 3.4/100,000 women. The prognosis is poor, especially once it recurs or metastasizes. Current therapeutic options include surgery, radio- and/or chemotherapy. Targeted therapy holds great promise of improving patient outcome while limiting toxicity and treatment exposure. Understanding the molecular cancer pathways of underlying HNSCC metastasis would help to improve the therapy of the disease. Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase (RTK) that can be activated by fibrillar collagens and implicated in several cancer cell behaviors, including VEGF expression, tumor angiogenesis, invasion, and metastasis. Matrix metalloproteinases (MMPs) are an important subset of downstream target genes of DDR2 signaling. Though previous studies have investigated the function of DDR2 in some common tumors, there has not been functional characterization of the potential role of DDR2 in HNSCC. Therefore, the aim of the current study was to investigate this issue. The general objective of this project is to verify the potential DDR2 gene as tumor markers and therapeutic target in HNSCC. In this study, DDR2 expression was examined by immunohistochemistry in 50 HNSCC patients, and the correlation between DDR2 expression with clinicopathologic factors was analyzed. The result showed DDR2 expression in all the nucleus, cytoplasm, and membrane in HNSCC patients. Statistical analysis revealed that DDR2 expression is associated with overall survival and recurrent-free survival. Patients with high DDR2 expression in the nucleus showed 6-fold higher risk of death compared to patients with a low level of DDR2 expression (p = 0,003) and 40-fold more chance of recurrence (p = 0,001). High DDR2 expression in the cytoplasm showed a 2.2-fold higher risk of death compared to patients with a low level (p = 0,026) and 47-fold more chance of recurrence (p = 0,006). In relation to plasma membrane, high DDR2 expression the results showed a 3.8-fold higher risk of death compared to patients with a low level (p = 0,008) and 6.5-fold more chance of recurrence (p = 0,009). In conclusion, these data suggest that DDR2 expression may be a prognostic indicator and a useful therapeutic target. Citation Format: Flavia Amoroso Matos e Silva, Katia Klug, Claudia Malheiros Coutinho-Camillo, Luiz Paulo Kowalski, Fernando Augusto Soares. DDR2 expression is associated with poor prognosis in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A036.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.