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Blockade of transforming growth factor β2 by anti-sense oligonucleotide improves immunotherapeutic potential of IL-2 against melanoma in a humanized mouse model.
- Source :
-
Cytotherapy [Cytotherapy] 2021 Jul; Vol. 23 (7), pp. 599-607. Date of Electronic Publication: 2021 May 09. - Publication Year :
- 2021
-
Abstract
- Background Aims: IL-2 is a potent cytokine that activates natural killer cells and CD8+ cytotoxic T lymphocytes (CTLs) and has been approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma. However, the medical use of IL-2 is restricted because of its narrow therapeutic window and potential side effects, including the expansion of regulatory T cells (Tregs).<br />Methods: In this study, the authors investigated the complementary effects of transforming growth factor-β2 (TGF-β2) anti-sense oligodeoxynucleotide (TASO) on the immunotherapeutic potential of IL-2 in a melanoma-bearing humanized mouse model.<br />Results: The authors observed that the combination of TASO and IL-2 facilitated infiltration of CTLs into the tumor, thereby potentiating the tumor killing function of CTLs associated with increased granzyme B expression. In addition, TASO attenuated the increase in Tregs by IL-2 in the peripheral blood and spleen and also inhibited infiltration of Tregs into the tumor, which was partly due to decreased CCL22. Alteration of T-cell constituents at the periphery by TGF-β2 inhibition combined with IL-2 might be associated with the synergistic augmentation of serum pro-inflammatory cytokines (such as interferon γ and tumor necrosis factor α) and decreased ratio of Tregs to CTLs in tumor tissues, which consequently results in significant inhibition of tumor growth CONCLUSIONS: These results indicate that the application of TASO improves IL-2-mediated anti-tumor immunity, thus implying that blockade of TGF-β2 in combination with IL-2 may be a promising immunotherapeutic strategy for melanoma.<br /> (Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1477-2566
- Volume :
- 23
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cytotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 33975794
- Full Text :
- https://doi.org/10.1016/j.jcyt.2021.01.003