T regulatory cells in cancer: recent advances and therapeutic potential.
BACKGROUND
The active suppression of immune responses against tumor is a major barrier to the likely success of cancer immunotherapy. There is now compelling evidence implicating T regulatory cells (Tregs) as being key players driving immune suppression. Elevated frequencies of Tregs within the peripheral circulation and tumor microenvironment of cancer patients correlate with poor prognosis and reduced survival. Understanding the mechanism of Treg elevation is critical for the development of new approaches aiming to modulate the frequency and function of Tregs to enhance the efficacy of cancer immune-based therapies.


METHODS
This review focuses on current knowledge concerning Tregs in cancer and discusses putative mechanisms which underlie the expansion of Tregs in cancer patients. Additionally, we review current strategies to deplete/suppress Treg activity, the limitations of these strategies and future perspective for improving their efficacy.


RESULTS
An insight of the current aspects concerning Treg subsets in cancer and an overview of recent advances in the identification of Treg-specific markers, in addition to the potential strategies to target Tregs for enhancing antitumor immunity.


CONCLUSIONS
Mechanisms by which Treg functions modulate the immune response to tumors are becoming further understood. However, specific markers to tumor-specific/induced Tregs are yet to be clearly identified, which is a major limitation in optimizing strategies to specifically target Tregs in cancer. Despite this, strategies aimed at modulating Tregs in patients are providing some early encouraging results supporting the overall concept and indicating that further studies are clearly warranted.
Elkord
Eyad
E
University of Salford, School of Environment and Life Sciences, Centre for Biochemistry, Drug Design and Cancer Research, Salford, UK. e.elkord@salford.ac.uk
Alcantar-Orozco
Erik M
EM
Dovedi
Simon J
SJ
Tran
Dat Q
DQ
Hawkins
Robert E
RE
Gilham
David E
DE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D000951:Antigens, Neoplasm / Q000276:immunology; D060908:CTLA-4 Antigen; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D051858:Forkhead Transcription Factors / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008212:Lymphocyte Depletion; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D015337:Multicenter Studies as Topic; D022423:Myeloid Cells / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide