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Intratumoral regulatory T cells: markers, subsets and their impact on anti‐tumor immunity
- Source :
- Immunology
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Regulatory T (Treg) cells play a crucial role in maintaining self‐tolerance and resolution of immune responses by employing multifaceted immunoregulatory mechanisms. However, Treg cells readily infiltrate into the tumor microenvironment (TME) and dampen anti‐tumor immune responses, thereby becoming a barrier to effective cancer immunotherapy. There has been a substantial expansion in the development of novel immunotherapies targeting various inhibitory receptors (IRs), such as CTLA4, PD1 and LAG3, but these approaches have mechanistically focused on the elicitation of anti‐tumor responses. However, enhanced inflammation in the TME could also play a detrimental role by facilitating the recruitment, stability and function of Treg cells by up‐regulating chemokines that promote Treg cell migration, and/or increasing inhibitory cytokine production. Furthermore, IR blockade may enhance Treg cell function and survival, thereby serving as a resistance mechanism against effective immunotherapy. Given that Treg cells are comprised of functionally and phenotypically heterogeneous sub‐populations that may alter their characteristics in a context‐dependent manner, it is critical to identify unique molecular pathways that are preferentially used by intratumoral Treg cells. In this review, we discuss markers that serve to identify certain Treg cell subsets, distinguished by chemokine receptors, IRs and cytokines that facilitate their migration, stability and function in the TME. We also discuss how these Treg cell subsets correlate with the clinical outcome of patients with various types of cancer and how they may serve as potential TME‐specific targets for novel cancer immunotherapies.
- Subjects :
- 0301 basic medicine
Chemokine
LAG3
medicine.medical_treatment
Immunology
chemical and pharmacologic phenomena
T-Lymphocytes, Regulatory
03 medical and health sciences
Chemokine receptor
Lymphocytes, Tumor-Infiltrating
0302 clinical medicine
Immune system
Review Series: Tregs in Cancer: Where are we now?
Cancer immunotherapy
Neoplasms
Tumor Microenvironment
medicine
Animals
Humans
Immunology and Allergy
Tumor microenvironment
biology
Immunotherapy
Phenotype
030104 developmental biology
Cytokine
Cancer research
biology.protein
Receptors, Chemokine
Tumor Escape
Chemokines
Inflammation Mediators
Signal Transduction
030215 immunology
Subjects
Details
- ISSN :
- 13652567 and 00192805
- Volume :
- 157
- Database :
- OpenAIRE
- Journal :
- Immunology
- Accession number :
- edsair.doi.dedup.....8a9387cae7c1c62aab2add0d622c03b9