TY - JOUR
T1 - The interplay of effector and regulatory T cells in cancer
AU - Roychoudhuri, Rahul
AU - Eil, Robert L.
AU - Restifo, Nicholas P.
N1 - Funding Information:
Thus, complex regulation of IL-2 and its high-affinity receptor IL-2Rα results in the potential for bistability in T reg and T eff cell population dynamics within tumors. First, an immunosuppressive state exists where T reg cells are supported by IL-2-producing T eff cells constrained in intermediate states of differentiation ( Figure 2 a). This immunosuppressive state predominates during the escape phase of tumor development. Second, an activated immune state exists, in which unrestrained T eff cell differentiation results in withdrawal of paracrine IL-2 support and competition for remaining IL-2 through antigen-driven expression of IL-2Rα ( Figure 2 b). While this state is rarely achieved spontaneously following tumor escape, such conditions may be achieved following therapeutic intervention (discussed below). The potential for IL-2 competition to account for population bistability is supported by mathematical models [ 68–70 ].
Publisher Copyright:
© 2015 Published by Elsevier Ltd.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Regulatory T (Treg) cells suppress effector T (Teff) cells and prevent immune-mediated rejection of cancer. Much less appreciated are mechanisms by which Teff cells antagonize Treg cells. Herein, we consider how complex reciprocal interactions between Teff and Treg cells shape their population dynamics within tumors. Under states of tolerance, including during tumor escape, suppressed Teff cells support Treg cell populations through antigen-dependent provision of interleukin (IL)-2. During immune activation, Teff cells can lose this supportive capacity and directly antagonize Treg cell populations to neutralize their immunosuppressive function. While this latter state is rarely achieved spontaneously within tumors, we propose that therapeutic induction of immune activation has the potential to stably disrupt immunosuppressive population states resulting in durable cancer regression.
AB - Regulatory T (Treg) cells suppress effector T (Teff) cells and prevent immune-mediated rejection of cancer. Much less appreciated are mechanisms by which Teff cells antagonize Treg cells. Herein, we consider how complex reciprocal interactions between Teff and Treg cells shape their population dynamics within tumors. Under states of tolerance, including during tumor escape, suppressed Teff cells support Treg cell populations through antigen-dependent provision of interleukin (IL)-2. During immune activation, Teff cells can lose this supportive capacity and directly antagonize Treg cell populations to neutralize their immunosuppressive function. While this latter state is rarely achieved spontaneously within tumors, we propose that therapeutic induction of immune activation has the potential to stably disrupt immunosuppressive population states resulting in durable cancer regression.
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U2 - 10.1016/j.coi.2015.02.003
DO - 10.1016/j.coi.2015.02.003
M3 - Review article
C2 - 25728990
AN - SCOPUS:84923686879
SN - 0952-7915
VL - 33
SP - 101
EP - 111
JO - Current opinion in immunology
JF - Current opinion in immunology
ER -