Immune Regulation by Self-Recognition: Novel Possibilities for Anticancer Immunotherapy

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 -