Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy.

By Helen Y Wang, Dean Anthony Lee, Guangyong Peng, Zhong Guo, Yanchun Li, Y. Kiniwa, E. Shevach, Rong‐Fu Wang. Immunity, 2004

599 citations recorded by the source corpus.

Regulatory T cells play an important role in the maintenance of immunological self-tolerance by suppressing immune responses against autoimmune diseases and cancer. Little is known, however, about the nature of the physiological target antigens for CD4(+) regulatory T (Treg) cells. Here we report the identification of the LAGE1 protein as a ligand for tumor-specific CD4(+) Treg cell clones generated from the tumor-infiltrating lymphocytes (TILs) of cancer patients. Phenotypic and functional analyses demonstrated that they were antigen-specific CD4(+) Treg cells expressing CD25 and GITR molecules and possessing suppressive activity on the proliferative response of naive CD4(+) T cells to anti-CD3 antibody stimulation. Ligand-specific activation and cell-cell contact were required for TIL102 Treg cells to exert suppressive activity on CD4(+) effector cells. These findings suggest that the presence of tumor-specific CD4(+) Treg cells at tumor sites may have a profound effect on the inhibition of T cell responses against cancer.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/597cfdfbff5efdef478aa3c223d2eb1e22561b70

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Citations in the corpus

• Tumor‐induced tolerance and immune suppression by myeloid derived suppressor cells (2008, background): “Treg cells are supposed to be headers of tolerance via a TCR repertoire aimed at recognizing self-antigens (135), including TAAs such as melanoma antigens (136).”
• Foxp3 Expressing CD4+CD25high Regulatory T Cells Are Overrepresented in Human Metastatic Melanoma Lymph Nodes and Inhibit the Function of Infiltrating T Cells1 (2004, background): “In favor of an Ag-driven stimulation of infiltrating Treg in melanoma, Wang’s group (50) recently identified the tumor Ag LAGE-1 as the ligand recognized by some infiltrating regulatory T cell clones isolated not from metastatic LNs but from a melanoma tumor.”