The interplay of effector and regulatory T cells in cancer.
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.
National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: roychoudhuri@mail.nih.gov.
Rahul
R
Roychoudhuri
National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA.
Robert L
RL
Eil
National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: restifo@nih.gov.
Nicholas P
NP
Restifo
D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation; D006649:Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D019899:Paracrine Communication; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D006649:Histocompatibility Antigens; D007376:Interleukin-2