Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 120 (12), 2417-27

Depletion of Radio-Resistant Regulatory T Cells Enhances Antitumor Immunity During Recovery From Lymphopenia

Affiliations

Depletion of Radio-Resistant Regulatory T Cells Enhances Antitumor Immunity During Recovery From Lymphopenia

Junko Baba et al. Blood.

Abstract

Cytotoxic lymphodepletion therapies augment antitumor immune responses. The generation and therapeutic efficacy of antitumor effector T cells (T(E)s) are enhanced during recovery from lymphopenia. Although the effects of lymphodepletion on naive T cells (T(N)s) and T(E)s have been studied extensively, the influence of lymphodepletion on suppressor cells remains poorly understood. In this study, we demonstrate a significant increase of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in sublethally irradiated lymphopenic mice. These radio-resistant Tregs inhibited the induction of T(E)s in tumor-draining lymph-nodes (TDLNs) during recovery from lymphopenia. The transfer of T(N)s into lymphopenic tumor-bearing mice resulted in some antitumor effects; however, Treg depletion after whole-body irradiation and reconstitution strongly inhibited tumor progression. Further analyses revealed that tumor-specific T cells were primed from the transferred T(N)s, whereas the Tregs originated from irradiated recipient cells. As in irradiated lymphopenic mice, a high percentage of Tregs was observed in cyclophosphamide-treated lymphopenic mice. The inhibition of Tregs in cyclophosphamide-treated mice significantly reduced tumor growth. These results indicate that the Tregs that survive cytotoxic therapies suppress antitumor immunity during recovery from lymphopenia and suggest that approaches to deplete radio and chemo-resistant Tregs can enhance cancer immunotherapies.

Comment in

  • Stubborn Tregs Limit T-cell Therapy
    CA Klebanoff et al. Blood 120 (12), 2352-4. PMID 22996654.
    In this issue of Blood, Baba and colleagues characterize a residual pool ofCD4+CD25+Foxp3+ regulatory T cells (Tregs) surviving a nonmyeloablative conditioning regimen th …

Similar articles

See all similar articles

Cited by 18 PubMed Central articles

  • Turning the Tide Against Regulatory T Cells
    S Han et al. Front Oncol 9, 279. PMID 31058083. - Review
    Regulatory T (Treg) cells play crucial roles in health and disease through their immunosuppressive properties against various immune cells. In this review we will focus o …
  • Genetic Redirection of T Cells for the Treatment of Pancreatic Cancer
    AI Ali et al. Front Oncol 9, 56. PMID 30809507. - Review
    Conventional treatments for pancreatic cancer are largely ineffective, and the prognosis for the vast majority of patients is poor. Clearly, new treatment options are des …
  • miRNA miR-21 Is Largely Dispensable for Intrathymic T-Cell Development
    H Kunze-Schumacher et al. Front Immunol 9, 2497. PMID 30455689.
    Development of T cells in the thymus is tightly controlled to continually produce functional, but not autoreactive, T cells. miRNAs provide a layer of post-transcriptiona …
  • Combining Immune Checkpoint Inhibitors With Conventional Cancer Therapy
    Y Yan et al. Front Immunol 9, 1739. PMID 30100909. - Review
    Immune checkpoint inhibitors (ICIs) have recently revolutionized cancer treatment, providing unprecedented clinical benefits. However, primary or acquired therapy resista …
  • The Pharmacology of T Cell Therapies
    MC Milone et al. Mol Ther Methods Clin Dev 8, 210-221. PMID 29552577. - Review
    Adoptive cellular therapy using T cells with tumor specificity derived from either natural T cell receptors (TCRs) or an artificial chimeric antigen receptor (CAR) has re …
See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources

Feedback