Perturbation of the normal immune system in patients with CLL
Perturbation of the normal immune system in patients with CLL
Immune dysregulation is a cardinal feature of chronic lymphocytic leukemia (CLL) from its early stage and worsens during clinical observation, even in absence of disease progression. Although the mechanisms remain unclear, new insights are emerging into the complex relationship between the CLL clone and its immune environment. T cells are increased in early-stage disease and show progressive accumulation and exhaustion. The mechanisms that drive this expansion may include auto-antigens involved in the original clonal expansion. In addition, chronic viral infections such as cytomegalovirus generate huge virus-specific immune responses, which are further expanded in CLL. Attention is now focused largely on the direct immunosuppressive properties of the tumor. Remarkably, CLL clones often have features of the recently described regulatory B cells producing immunosuppressive IL-10. Better knowledge of the regulatory properties intrinsic to CLL cells may soon become more important with the switch from chemotherapy-based treatments, which trade control of CLL with further impairment of immune function, to the new agents targeting CLL B-cell receptor-associated signaling. Treatment with these new agents is associated with evidence of immune recovery and reduced infectious complications. As such, they offer the prospect of immunologic rehabilitation and a platform from which to ultimately replace chemotherapy
573-581
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Moss, Paul
9b1abef3-0b2f-4cd0-b3be-49629c95bd18
30 July 2015
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Moss, Paul
9b1abef3-0b2f-4cd0-b3be-49629c95bd18
Abstract
Immune dysregulation is a cardinal feature of chronic lymphocytic leukemia (CLL) from its early stage and worsens during clinical observation, even in absence of disease progression. Although the mechanisms remain unclear, new insights are emerging into the complex relationship between the CLL clone and its immune environment. T cells are increased in early-stage disease and show progressive accumulation and exhaustion. The mechanisms that drive this expansion may include auto-antigens involved in the original clonal expansion. In addition, chronic viral infections such as cytomegalovirus generate huge virus-specific immune responses, which are further expanded in CLL. Attention is now focused largely on the direct immunosuppressive properties of the tumor. Remarkably, CLL clones often have features of the recently described regulatory B cells producing immunosuppressive IL-10. Better knowledge of the regulatory properties intrinsic to CLL cells may soon become more important with the switch from chemotherapy-based treatments, which trade control of CLL with further impairment of immune function, to the new agents targeting CLL B-cell receptor-associated signaling. Treatment with these new agents is associated with evidence of immune recovery and reduced infectious complications. As such, they offer the prospect of immunologic rehabilitation and a platform from which to ultimately replace chemotherapy
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Accepted/In Press date: 8 June 2015
e-pub ahead of print date: 17 June 2015
Published date: 30 July 2015
Organisations:
Cancer Sciences
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Local EPrints ID: 380235
URI: http://eprints.soton.ac.uk/id/eprint/380235
ISSN: 0006-4971
PURE UUID: 4087015c-2b76-4d4e-9c40-9e6ff6b09dc3
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Date deposited: 04 Sep 2015 14:55
Last modified: 15 Mar 2024 03:41
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Author:
Paul Moss
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