CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
artículos
Título:
Interleukin-7 inhibits tumor-induced CD27-CD28- suppresor T cells: implications for cancer immunotherapy
Autor/es:
YUE ZHANG; LUKAS W PFANNENSTIEL ; ELZBIETA BOLESTA; CAROLINA MONTES; XIAOYU ZHANG; ANDREI I. CHOPAVAL; RONALD GARTENHAUS ; SCOTT E. STROME; BRIAN R. GASTMAN
Revista:
CLINICAL CANCER RESEARCH
Editorial:
AMER ASSOC CANCER RESEARCH
Referencias:
Año: 2011 p. 4975 - 4986
ISSN:
1078-0432
Resumen:
Evasion of immune recognition by tumor cells is understood to be a key part of
carcinogenesis. We have previously reported that many types of tumors are able to
induce changes in human T cells that lead to the acquisition of suppressive function as
well as phenotypic alterations resembling those found in senescent T cells. Importantly
these same T cells were reported to be elevated in the peripheral blood of cancer patients.
In the present study we show that IL-7 inhibits this process and maintains T cell
proliferative capacity, IL-2 production, and reduces suppressive function. This protective
ability of IL-7 depends on activation of the PI3K/AKT pathway, which then inhibits
activation of glycogen synthase kinase 3â (GSK3â) and subsequently prevents the
phosphorylation and loss of Mcl-1. We further demonstrate a key role for Mcl-1 in that
its knock-down or inhibition abrogates the effects of IL-7. Additionally, knock-down of
the Mcl-1 binding partner and pro-apoptotic protein Bim protects T cells from these
alterations. Collectively, these observations confirm the role for Bcl-2 family members
in cytokine signaling, and suggest that IL-7 treatment in combination with other
immunotherapies could lead to new clinical strategies to maintain normal T cell function
and reduce tumor-induced generation of dysfunctional and suppressor T cells.â (GSK3â) and subsequently prevents the
phosphorylation and loss of Mcl-1. We further demonstrate a key role for Mcl-1 in that
its knock-down or inhibition abrogates the effects of IL-7. Additionally, knock-down of
the Mcl-1 binding partner and pro-apoptotic protein Bim protects T cells from these
alterations. Collectively, these observations confirm the role for Bcl-2 family members
in cytokine signaling, and suggest that IL-7 treatment in combination with other
immunotherapies could lead to new clinical strategies to maintain normal T cell function
and reduce tumor-induced generation of dysfunctional and suppressor T cells.