2024-03-29T11:19:38Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00023126
2023-01-16T05:05:53Z
499:500:501
Roles of regulatory T cells in cancer immunity
Takeuchi, Yoshiko
Nishikawa, Hiroyoshi
open access
This is a pre-copyedited, author-produced version of an article accepted for publication in [International Immunology] following peer review. The version of record [International Immunology. v.28, n.8, 2016, p.401-409] is available online at: http://doi.org/10.1093/intimm/dxw025.
immune suppression
immune checkpoint inhibitors
Treg-targeted therapy
CD4+ regulatory T cells (Tregs) expressing the transcription factor FoxP3 are highly immune suppressive and play central roles in the maintenance of self-tolerance and immune homeostasis, yet in malignant tumors they promote tumor progression by suppressing effective antitumor immunity. Indeed, higher infiltration by Tregs is observed in tumor tissues, and their depletion augments antitumor immune responses in animal models. Additionally, increased numbers of Tregs and, in particular, decreased ratios of CD8+ T cells to Tregs among tumor-infiltrating lymphocytes are correlated with poor prognosis in various types of human cancers. The recent success of cancer immunotherapy represented by immune checkpoint blockade has provided a new insight in cancer treatment, yet more than half of the treated patients did not experience clinical benefits. Identifying biomarkers that predict clinical responses and developing novel immunotherapies are therefore urgently required. Cancer patients whose tumors contain a large number of neoantigens stemming from gene mutations, which have not been previously recognized by the immune system, provoke strong antitumor T-cell responses associated with clinical responses following immune checkpoint blockade, depending on the resistance to Treg-mediated suppression. Thus, integration of a strategy restricting Treg-mediated immune suppression may expand the therapeutic spectrum of cancer immunotherapy towards patients with a lower number of neoantigens. In this review, we address the current understanding of Treg-mediated immune suppressive mechanisms in cancer, the involvement of Tregs in cancer immunotherapy, and strategies for effective and tolerable Treg-targeted therapy.
Oxford University Press
2016-08
eng
journal article
AM
http://hdl.handle.net/2237/25320
https://nagoya.repo.nii.ac.jp/records/23126
https://doi.org/10.1093/intimm/dxw025
0953-8178
International Immunology
28
8
401
409
https://nagoya.repo.nii.ac.jp/record/23126/files/s1-ln234847841682381206-1939656818Hwf-2035235115IdV16389160123484784PDF_HI0001.pdf
application/pdf
1.2 MB
2017-08-01