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Topical treatment of all‐ trans retinoic acid inhibits murine melanoma partly by promoting CD8 + T‐cell immunity
Author(s) -
Yin Wei,
Song Yan,
Liu Qing,
Wu Yunyun,
He Rui
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12768
Subject(s) - cd8 , tretinoin , retinoic acid , cancer research , melanoma , biology , cytotoxic t cell , foxp3 , immunology , microbiology and biotechnology , chemistry , immune system , cell culture , biochemistry , in vitro , genetics
Summary All‐ trans retinoic acid (at RA ), 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 humans indicates the beneficial role of at RA in melanoma. However, it remains unknown whether topical application of at RA could inhibit melanoma growth by influencing tumour immunity. We demonstrate topical application of tretinoin ointment (at RA as the active ingredient) effectively inhibited B16F10 melanoma growth. This is accompanied by markedly enhanced CD 8 + T‐cell responses, as evidenced by significantly increased proportions of effector CD 8 + T cells expressing granzyme B, tumour necrosis factor‐ α , or interferon‐ γ , and Ki67 + proliferating CD 8 + T cells in at RA ‐treated tumours compared with vaseline controls. Furthermore, topical at RA treatment promoted the differentiation of effector CD 8 + T cells in draining lymph nodes ( DLN ) of tumour‐bearing mice. Interestingly, at RA did not affect tumoral CD 4 + T‐cell response, and even inhibited the differentiation of interferon‐ γ ‐expressing T helper type 1 cells in DLN . Importantly, we demonstrated that the tumour‐inhibitory effect of at RA was partly dependent on CD 8 + T cells, as CD 8 + T‐cell depletion restored tumour volumes in at RA ‐treated mice, which, however, was still significantly smaller than those in vaseline‐treated mice. Finally, we demonstrated that at RA up‐regulated MHCI expression in B16F10 cells, and DLN cells from tumour‐bearing mice had a significantly higher killing rate when culturing with at RA ‐treated B16F10 cells. Hence, our study demonstrates that topical at RA treatment effectively inhibits melanoma growth partly by promoting the differentiation and the cytotoxic function of effector CD 8 + T cells.