Topical treatment of All-trans Retinoic Acid inhibits murine melanoma partly by promoting CD8+ T cell immunity

Published on Friday, 02 June 2017


All-trans retinoic acid (atRA), the main biologically active metabolite of vitamin A, has been implicated in immunoregulation and anti-cancer. A recent finding that vitamin A could decrease the risk of melanoma in human indicates the beneficial role of atRA in melanoma. However, it remains unknown whether topical application of atRA could inhibit melanoma growth by influencing tumor immunity.

We here demonstrated topical application of tretinoin ointment (atRA as the active ingredient) effectively inhibited B16F10 melanoma growth. This is accompanied by markedly enhanced CD8+ T cell responses, as evidenced by significantly increased proportions of effector CD8+ T cells that expressing granzyme B, TNF-α, or IFN-γ, and Ki67+ proliferating CD8+ T cells in atRA-treated tumors compared with vaseline controls.

Furthermore, topical atRA treatment promoted the differentiation of effector CD8+ T cells in draining lymph nodes (DLN) of tumor-bearing mice. Interestingly, atRA did not affect tumoral CD4+ T cell response, and even inhibited the differentiation of IFN-γ-expressing Th1 cells in DLN.

Importantly, we demonstrated that the tumor-inhibitory effect of atRA was partly dependent on CD8+ T cells, as CD8+ T cell depletion restored tumor volumes in atRA-treated mice, which, however, was still significantly smaller than those in vaseline-treated mice.

Finally, we demonstrated that atRA up-regulated MHCI expression in B16F10 cells, and DLN cells from tumor-bearing mice had a significantly higher killing rate when culturing with atRA-treated B16F10 cells.

Thus, our study demonstrates topical atRA treatment effectively inhibits melanoma growth partly by promoting the differentiation and the cytotoxic function of effector CD8+ T cells.



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See also:

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonisn, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.