Targeting Regulatory T Cells in Cancer

Byrne, William L.; Mills, Kingston H. G.; Lederer, James A.; O’Sullivan, Gerald C.

doi:10.1158/0008-5472.can-11-1156

Cited by 174 publications

(143 citation statements)

References 33 publications

Supporting

Mentioning

138

Contrasting

Unclassified

Order By: Relevance

“…Los tumores adicionalmente liberan IDO, adenosina, que es producto de la hipoxia del ambiente tumoral, y que promueve las Treg, así como la producción de CCL28 favoreciendo su inmigración. En este sentido, es congruente también la asociación entre inmunodeficiencia asociada a transplantes y aumento en la prevalencia de cáncer [30][31][32][33]38 .…”

Section: Escapeunclassified

Las Dos Caras De La Inmunidad: Respuesta Th

Velarde¹

2016

RFMH

View full text Add to dashboard Cite

RESUMENObjetivos: Las citokinas poseen una acción pleiotrópica que intervienen tanto en la salud como en la enfermedad, que es mediado por la respuesta linfocitaria T helper. Existe una interacción no excluyente entre la respuesta Th efectora/reguladora, de la cual depende el éxito de procesos fisiológicos y fisiopatológicos en su disregulación. En esta revisión, mencionaremos algunos ejemplos representativos de la disregulación Th. En el embarazo recae en una respuesta inicial mediada por Th1, y en su defecto ocurren mecanismos relacionados a la preeclampsia. Un disbalance con predominio Th2 es descrito en el asma, pero por otro lado es una respuesta relacionada a la sobrevida de un injerto en el transplante de órganos. Asimismo, mecanismos relacionados a un déficit Th1 subyacen en el modelo inmunogénico del cáncer. De la comprensión de este equilibrio se desprende la capacidad de modificar los diferentes escenarios clínicos en un concepto inmunológico.Palabras clave: Citokinas,Th; Preeclampsia; Transplante; Cáncer; Asma. (fuente: DeCS BIREME) ABSTRACTObjective: Cytokines have pleiotropic action involving health and disease through T helper lymphocyte response. An interactive response effector/regulatory or Th response, is related with physiological and pathophysiological processes. Pregnancy has an initial response mediated by Th1, but in lack response, there are mechanisms related to preeclampsia. A predominant Th2 imbalance is described in asthma, however, this response is related to a graft survival of transplanted organs. Mechanisms related to a deficit Th1 is regard to the inmunogenic cancer model. Understanding this balance is important to modify clinical contexts with an immunological concept.

show abstract

Section: Escapeunclassified

Las Dos Caras De La Inmunidad: Respuesta Th

Velarde¹

2016

RFMH

View full text Add to dashboard Cite

show abstract

“…For both CD4  and CD8  effector T cells, TiM-3 represents a pivotal target and moreover either subset CD4  or CD8  effector T cells alone is capable of remarkable antitumor activity [79,80]. For example, TiM-3  CD4 T cells accumulate in human tumor tissues and produce lower levels of Th1-type cytokines whereas express higher levels of CD25, Foxp3, CTLA-4 and giTR [69].…”

Section: Expression and Inhibitory Role In Immune Response Of Tim-3mentioning

confidence: 99%

“…The mechanism might be the reduction of the immunosuppressive functions of TiM-3  Tregs and the alteration of their homing to and/or retention within neoplastic lesions [81], based on that the most exhausted population of CD8  T cells is marked by the expression of both TiM-3 and PD-1 73. At the gene level, a few genes including Runx1, iRF5 and iRF7 are upregulated in response to the coblockade of TiM-3-and PD-1-transduced signals in vivo [79]. Furthermore, combined with anti-CTLA-4/PD-1/ PD-L1 antibodies, TiM-3 blockade can remarkably suppress tumor growth in animal models [73,93,94].…”

Section: Expression and Inhibitory Role In Immune Response Of Tim-3mentioning

confidence: 99%

Emerging immune checkpoints for cancer therapy

Zheng

et al. 2015

Acta Oncologica

View full text Add to dashboard Cite

background. Immunotherapy with immune checkpoint inhibitors has emerged as promising treatment modality for cancer based on the success of anti-CTLA-4 and -PD-1/PD-L1 antibodies. LAG-3 and TIM-3 are two new immune checkpoints. The aim of this work is to review the role and application of LAG-3 and TIM-3 for cancer immunotherapy. Material and methods. Literatures were searched and collected in Medline/PubMed. results. LAG-3 is presented as a CD4 homolog type I transmembrane protein which binds MHC class II molecules. LAG-3 negatively regulates T cell proliferation, homeostasis and function. IMP321 is formed of an extracellular portion of human LAG-3 fused to the Fc fraction of human IgG1 and has shown increased T cell responses and tolerability in phase I studies on advanced renal cell cancer. When combined with paclitaxel, IMP321 has exerted immune enhancement and tumor inhibition with no significant IMP321-related adverse events. TIM-3 belongs to the TIM family and mainly negatively regulates Th1 immunity. The TIM-3/galectin-9 pathway contributes to the suppressive tumor microenvironment. TIM-3 overexpression is associated with poor prognosis in a variety of cancers. Both LAG-3 and TIM-3 are coexpressed with other immune checkpoints. The application of LAG-3 or TIM-3 does play an important role in anti-tumor responses, and maybe better when combing with anti-CTLA-4 and anti-PD-1/L1 antibodies. conclusions. These two immune checkpoints play crucial roles in cancer development and may be used in future clinical practice of cancer therapy.

show abstract

“…T regs are concentrated in the tumor mass during earlier stages of tumor development, leading to immune escape of the tumor from robust antitumor immune response. Thus, primary tumor can progress due to local inhibition of effector immune responses, but metastatic cells are eliminated by active systemic immune response [168]. CD4 + T cells, which highly express CD25 and play an important role in the suppression and prevention of autoimmunity, are referred as T regs [169].…”

Section: Regulatory T Cells In Tumor Microenvironmentmentioning

confidence: 99%

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

Kumar

2012

Purinergic Signalling

View full text Add to dashboard Cite

Cancer is a chronic disease and its pathogenesis is well correlated with infection and inflammation. Adenosine is a purine nucleoside, which is produced under metabolic stress like hypoxic conditions. Acute or chronic inflammatory conditions lead to the release of precursor adenine nucleotides (adenosine triphosphate (ATP), adenosien diphosphate (ADP) and adenosine monophosphate (AMP)) from cells, which are extracellularly catabolized into adenosine by extracellular ectonucleotidases, i.e., CD39 or nucleoside triphosphate dephosphorylase (NTPD) and CD73 or 5′-ectonucleotidase. It is now well-known that adenosine is secreted by cancer as well as immune cells during tumor pathogenesis under metabolic stress or hypoxia. Once adenosine is released into the extracellular environment, it exerts various immunomodulatory effects via adenosine receptors (A 1 , A 2A , A 2B , and A 3 ) expressed on various immune cells (i.e., macrophages, myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, dendritic cells (DCs), T cells, regulatory T cell (T regs ), etc.), which play very important roles in the pathogenesis of cancer. This review is intended to summarize the role of inflammation and adenosine in the immunopathogenesis of tumor along with regulation of tumor-specific immune response and its modulation as an adjunct approach to tumor immunotherapy.

show abstract

Targeting Regulatory T Cells in Cancer

Cited by 174 publications

References 33 publications

Las Dos Caras De La Inmunidad: Respuesta Th

Las Dos Caras De La Inmunidad: Respuesta Th

Emerging immune checkpoints for cancer therapy

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

Contact Info

Product

Resources

About