TY - JOUR
T1 - Immune Regulation by Self-Recognition
T2 - Novel Possibilities for Anticancer Immunotherapy
AU - Andersen, Mads Hald
N1 - © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected].
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Circulating T cells that specifically target normal self-proteins expressed by regulatory immune cells were first described in patients with cancer, but can also be detected in healthy individuals. The adaptive immune system is distinguished for its ability to differentiate between self-antigens and foreign antigens. Thus, it was remarkable to discover T cells that apparently lacked tolerance to important self-proteins, eg, IDO, PD-L1, and FoxP3, expressed in regulatory immune cells. The ability of self-reactive T cells to react to and eliminate regulatory immune cells can influence general immune reactions. This suggests that they may be involved in immune homeostasis. It is here proposed that these T cells should be termed antiregulatory T cells (anti-Tregs). The role of anti-Tregs in immune-regulatory networks may be diverse. For example, pro-inflammatory self-reactive T cells that react to regulatory immune cells may enhance local inflammation and inhibit local immune suppression. Further exploration is warranted to investigate their potential role under different malignant conditions and the therapeutic possibilities they possess. Utilizing anti-Tregs for anticancer immunotherapy implies the direct targeting of cancer cells in addition to regulatory immune cells. Anti-Tregs provide the immune system with yet another level of immune regulation and contradict the notion that immune cells involved in the adjustment of immune responses only act as suppressor cells.
AB - Circulating T cells that specifically target normal self-proteins expressed by regulatory immune cells were first described in patients with cancer, but can also be detected in healthy individuals. The adaptive immune system is distinguished for its ability to differentiate between self-antigens and foreign antigens. Thus, it was remarkable to discover T cells that apparently lacked tolerance to important self-proteins, eg, IDO, PD-L1, and FoxP3, expressed in regulatory immune cells. The ability of self-reactive T cells to react to and eliminate regulatory immune cells can influence general immune reactions. This suggests that they may be involved in immune homeostasis. It is here proposed that these T cells should be termed antiregulatory T cells (anti-Tregs). The role of anti-Tregs in immune-regulatory networks may be diverse. For example, pro-inflammatory self-reactive T cells that react to regulatory immune cells may enhance local inflammation and inhibit local immune suppression. Further exploration is warranted to investigate their potential role under different malignant conditions and the therapeutic possibilities they possess. Utilizing anti-Tregs for anticancer immunotherapy implies the direct targeting of cancer cells in addition to regulatory immune cells. Anti-Tregs provide the immune system with yet another level of immune regulation and contradict the notion that immune cells involved in the adjustment of immune responses only act as suppressor cells.
KW - CD4-Positive T-Lymphocytes
KW - CD8-Positive T-Lymphocytes
KW - Forkhead Transcription Factors
KW - Humans
KW - Immune System
KW - Immunotherapy
KW - Indoleamine-Pyrrole 2,3,-Dioxygenase
KW - Inflammation
KW - Molecular Targeted Therapy
KW - Neoplasms
KW - T-Lymphocytes
KW - T-Lymphocytes, Regulatory
KW - Tryptophan Oxygenase
U2 - 10.1093/jnci/djv154
DO - 10.1093/jnci/djv154
M3 - Comment/debate
C2 - 26063792
SN - 1460-2105
VL - 107
SP - 1
EP - 8
JO - National Cancer Institute. Journal (Online)
JF - National Cancer Institute. Journal (Online)
IS - 9
M1 - djv154
ER -
