Expression of the Tigit/CD226/CD155 Receptors/Ligand System in Chronic Lymphocytic Leukemia in Blood
2019
AOU Città della Salute di Torino
Tipo pubblicazione
Conference Abstract
Autori/Collaboratori (9)Vedi tutti...
Arruga F
Department of Medical Sciences, University of Torino, Turin, Italy
Guerra G
Department of Medical Sciences, University of Torino, Turin, Italy
Baev D
Italian Institute for Genomic Medicine, Torino, Italy
et alii...
Abstract
Introduction: T cell immunoreceptor with Ig and ITIM domains (TIGIT) is a surface receptor mainly expressed by CD8+, regulatory T lymphocytes and natural killer (NK) cells, but not by normal B cells. It performs as an inhibitory immune checkpoint, activated through binding of CD155. TIGIT competes with CD226 for CD155 binding, resulting in opposite outcomes: while CD226 enhances cytotoxicity of T lymphocytes and NK cells, TIGIT exerts immunosuppressive effects. Whether TIGIT engagement triggers an alternative signaling cascade, or whether it simply prevents CD226 activation, remains an open point. Tumor-infiltrating T lymphocytes generally express high levels of the molecule, together with the other checkpoint inhibitor PD-1. On this basis, antagonist antibodies targeting TIGIT are under evaluation to restore immunity and treat cancer patients, alone or in various combinations. Chronic lymphocytic leukemia (CLL), the most common adult leukemia, is characterized by a highly heterogeneous clinical outcome. Several molecular markers can help in stratifying patients, including the presence or absence of somatic mutations in B cell receptor, cytogenetic aberrations and single gene mutations. Interestingly, CLL cells express several T cell specific antigens, including CD5. A previous report indicates that, in CLL, TIGIT is expressed by circulating CD4+T cells, increasing during disease progression, while nothing is known about its expression on CLL cells. Aim:This work was undertaken with the aim of studying expression of the TIGIT/CD226/CD155 axis in CLL. Methods:We assembled a cohort of 101 primary CLL samples (40% females, mean age of 61). All patients were either untreated or had not received treatment in the 6 months prior to analysis. PBMC samples were tested for expression of TIGIT, CD155 and CD226 in both T and B subsets. A multiparametric flow cytometry strategy was designed, combining anti-TIGIT, anti-CD155 and anti-CD226 antibodies with a panel of B- (an
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DOI : 10.1182/blood-2019-128308
Keywords
5' nucleotidase; ADP ribosyl cyclase/cyclic ADP ribose hydrolase 1; alpha4 integrin; B lymphocyte receptor; CD14 antigen; CD19 antigen; CD3 antibody; CD4 antibody; CD4 antigen; CD5 antigen; CD56 antigen; CD8 antigen; endogenous compound; molecular marker; Notch1 receptor; programmed death 1 receptor; adult; advanced cancer; advisory committee; antigen specificity; cancer patient; cancer staging; CD4+ T lymphocyte; cell population; chromosome aberration; chronic lymphatic leukemia; clinical outcome; cohort analysis; conference abstract; controlled study; employment; enzyme activity; female; flow cytometry; fluorescence intensity; funding; gender; gene mutation; human; human cell; human tissue; lymphocyte count; major clinical study; male; middle aged; natural killer cell mediated cytotoxicity; outcome assessment; peripheral blood mononuclear cell; protein expression; protein function; regulatory T lymphocyte; signal transduction; somatic mutation; trisomy 12;