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Programmed death 1 and B and T lymphocyte attenuator immunoreceptors and their association with malignant T‐lymphoproliferative disorders: brief review
Author(s) -
Karakatsanis Stamatis,
Bertsias George,
Roussou Paraskevi,
Boumpas Dimitrios
Publication year - 2014
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.2098
Subject(s) - btla , immune system , cytotoxic t cell , t cell , immunology , cd8 , lymphoproliferative disorders , lymphocyte , t lymphocyte , cancer research , biology , medicine , lymphoma , biochemistry , in vitro
Malignant T‐cell lymphoproliferative diseases are relatively rare. T cells are activated through the T‐cell receptor with the aid of costimulating molecules that can be either excitatory or inhibitory. Such pathways have been also implicated in mechanisms of malignant T‐cell lymphoproliferative diseases' persistence and relapse by circumventing immune responses. To date, three major immunoinhibitory molecules have been recognized, namely programmed cell death‐1 (PD‐1), B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte antigen 4 (CTLA‐4). Although CTLA‐4 is considered the ‘gatekeeper’ of immune tolerance, PD‐1 negatively regulates immune responses broadly, whereas BTLA activation has been shown to inhibit CD8+ cancer‐specific T cells. Both PD‐1 and BTLA downregulate proximal T‐cell receptor signalling cascade and are involved in immune evasion of leukaemias and lymphomas, even after allogeneic stem cell transplantation. These immunoregulatory molecules can have seemingly a synergistic effect on weakening the immune response of patients with haematological malignancies, and their manipulation represents a very active field of preclinical as well as clinical interest. Copyright © 2013 John Wiley & Sons, Ltd.