CD25

CD25 is the alpha chain of the IL-2 receptor. It is a type I transmembrane protein present on activated T cells, activated B cells, some thymocytes, myeloid precursors, and oligodendrocytes that associates with CD122 to form a heterodimer that can act as a high-affinity receptor for IL-2.

CD25 is expressed in most B-cell neoplasms, some acute nonlymphocytic leukemias, neuroblastomas, and tumor infiltrating lymphocytes. Its soluble form, called sIL-2R may be elevated in these diseases and is occasionally used to track disease progression.

Grauer et al. demonstrated a time-dependent accumulation of CD4+FoxP3+ Tregs in brain tumors with a syngeneic murine glioma GL261 model. They observed that the expression of CD25, CTLA-4, GITR, and CXCR4 on intratumoral CD4+FoxP3+ Treg during tumor growth is upregulated in a time-dependent manner. They also demonstrate that treatment with anti-CD25 MAbs significantly provokes a CD4 and CD8 T-cell-dependent destruction of glioma cells. Moreover, combining Treg depletion with administration of blocking CTLA-4 mAbs further boosted glioma-specific CD4+ and CD8+ effector T cells, as well as antiglioma IgG2a antibody titers, resulting in complete tumor eradication. This study illustrated that intratumoral accumulation and activation of CD4+FoxP3+ Tregs act as a dominant immune-escape mechanism for gliomas and underline the importance of controlling tumor-infiltrating Tregs in glioma immunotherapy.