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Critical Roles of Chemoresistant Effector and Regulatory T Cells in Antitumor Immunity after Lymphodepleting Chemotherapy.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Jul 15; Vol. 195 (2), pp. 726-35. Date of Electronic Publication: 2015 Jun 03. - Publication Year :
- 2015
-
Abstract
- Antitumor immunity is augmented by cytotoxic lymphodepletion therapies. Adoptively transferred naive and effector T cells proliferate extensively and show enhanced antitumor effects in lymphopenic recipients. Although the impact of lymphodepletion on transferred donor T cells has been well evaluated, its influence on recipient T cells is largely unknown. The current study demonstrates that both regulatory T cells (Tregs) and effector CD8(+) T cells from lymphopenic recipients play critical roles in the development of antitumor immunity after lymphodepletion. Cyclophosphamide (CPA) treatment depleted lymphocytes more efficiently than other cytotoxic agents; however, the percentage of CD4(+)CD25(+) Foxp3(+) Tregs was significantly increased in CPA-treated lymphopenic mice. Depletion of these chemoresistant Tregs following CPA treatment and transfer of naive CD4(+) T cells augmented the antitumor immunity and significantly suppressed tumor progression. Further analyses revealed that recipient CD8(+) T cells were responsible for this augmentation. Using Rag2(-/-) mice or depletion of recipient CD8(+) T cells after CPA treatment abrogated the augmentation of antitumor effects in CPA-treated reconstituted mice. The transfer of donor CD4(+) T cells enhanced the proliferation of CD8(+) T cells and the priming of tumor-specific CD8(+) T cells originating from the lymphopenic recipients. These results highlight the importance of the recipient cells surviving cytotoxic regimens in cancer immunotherapies.<br /> (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Subjects :
- Adoptive Transfer
Animals
Cisplatin pharmacology
Cyclophosphamide pharmacology
Deoxycytidine analogs & derivatives
Deoxycytidine pharmacology
Drug Resistance immunology
Etoposide pharmacology
Female
Fibrosarcoma chemically induced
Fibrosarcoma immunology
Fibrosarcoma pathology
Lymph Nodes immunology
Lymph Nodes pathology
Lymphopenia chemically induced
Lymphopenia immunology
Lymphopenia pathology
Methylcholanthrene
Mice
Mice, Inbred C57BL
Mice, Knockout
Paclitaxel pharmacology
T-Lymphocytes, Cytotoxic drug effects
T-Lymphocytes, Cytotoxic pathology
T-Lymphocytes, Regulatory drug effects
T-Lymphocytes, Regulatory pathology
Tumor Cells, Cultured
Vidarabine analogs & derivatives
Vidarabine pharmacology
Whole-Body Irradiation
Gemcitabine
Cytotoxins pharmacology
Fibrosarcoma therapy
Lymphocyte Depletion
Lymphopenia therapy
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 195
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 26041539
- Full Text :
- https://doi.org/10.4049/jimmunol.1401468