| Autor: |
Saxena R; Beth Israel Deaconess Medical Center, Boston., Wang Y; X4 Pharmaceuticals, Cambridge, Massachusetts, USA., Mier JW; Beth Israel Deaconess Medical Center, Boston. |
| Jazyk: |
angličtina |
| Zdroj: |
Melanoma research [Melanoma Res] 2020 Feb; Vol. 30 (1), pp. 14-25. |
| DOI: |
10.1097/CMR.0000000000000639 |
| Abstrakt: |
To determine whether blockade of the chemokine receptor CXCR4 might alter the tumor microenvironment and inhibit tumor growth, we tested the efficacy of the CXCR4 antagonist X4-136 as a single agent and in combination with various immune checkpoint inhibitors in the syngeneic murine melanoma model B16-OVA. We also tested its activity alone and in combination with axitinib in the renal cancer model Renca. We found that X4-136 exhibited potent single agent antitumor activity in the B16-OVA model that was additive to that of an anti-PDL1 antibody. The antitumor activities were associated with a reduction in the number of immunosuppressive regulatory T cells and myeloid-derived suppressor cells and an increase in the number of tumor-specific CD8/perforin cells in the tumor-microenvironment. Apart from these immune effects, X4-136 alone and in combination with checkpoint inhibitors inhibited the Akt/FOXO-3a cell survival pathway in vitro and in vivo, suggesting that it might have antitumor activity independent of its effects on immune cell trafficking. Similar effects on tumor growth and cytotoxic T lymphocytes infiltration were observed in the Renca model. These studies show that the effects of CXCR4 blockade on immune cell trafficking might serve as a useful adjunct to immune checkpoint inhibitors and other therapies in the treatment of cancer. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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