Coinhibitory molecules in hematologic malignancies: targets for therapeutic intervention.
Blood
; 120(4): 728-36, 2012 Jul 26.
Article
em En
| MEDLINE
| ID: mdl-22563087
ABSTRACT
The adaptive immune system can be a potent defense mechanism against cancer; however, it is often hampered by immune suppressive mechanisms in the tumor microenvironment. Coinhibitory molecules expressed by tumor cells, immune cells, and stromal cells in the tumor milieu can dominantly attenuate T-cell responses against cancer cells. Today, a variety of coinhibitory molecules, including cytotoxic T lymphocyte-associated antigen-4, programmed death-1, B and T lymphocyte attenuator, LAG3, T-cell immunoglobulin and mucin domain 3, and CD200 receptor, have been implicated in immune escape of cancer cells. Sustained signaling via these coinhibitory molecules results in functional exhaustion of T cells, during which the ability to proliferate, secrete cytokines, and mediate lysis of tumor cells is sequentially lost. In this review, we discuss the influence of coinhibitory pathways in suppressing autologous and allogeneic T cell-mediated immunity against hematologic malignancies. In addition, promising preclinical and clinical data of immunotherapeutic approaches interfering with negative cosignaling, either as monotherapy or in conjunction with vaccination strategies, are reviewed. Numerous studies indicate that coinhibitory signaling hampers the clinical benefit of current immunotherapies. Therefore, manipulation of coinhibitory networks is an attractive adjuvant immunotherapeutic intervention for hematologic cancers after standard treatment with chemotherapy and hematopoietic stem cell transplantation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Neoplasias Hematológicas
/
Tolerância Imunológica
Limite:
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Holanda