Interleukin-7 regulates CD127 expression and promotes CD8 + T cell activity in patients with primary cutaneous melanoma
Interleukin (IL)-7 signaling through CD127 is impaired in lymphocytes in cancers and chronic infections, resulting in CD8 T cell exhaustion. The mechanisms underlying CD8 T cell responses to IL-7 in melanoma remain not completely elucidated. We previously showed reduced IL-7 level in melanoma patien...
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Veröffentlicht in: | BMC immunology 2022-07, Vol.23 (1), p.35-35, Article 35 |
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Zusammenfassung: | Interleukin (IL)-7 signaling through CD127 is impaired in lymphocytes in cancers and chronic infections, resulting in CD8
T cell exhaustion. The mechanisms underlying CD8
T cell responses to IL-7 in melanoma remain not completely elucidated. We previously showed reduced IL-7 level in melanoma patients. Thus, the aim of this study was to investigate the effect of IL-7 regulation on CD127 expression and CD8
T cell responses in melanoma.
Healthy controls and primary cutaneous melanoma patients were enrolled. Membrane-bound CD127 (mCD127) expression on CD8
T cells was determined by flow cytometry. Soluble CD127 (sCD127) protein level was measured by ELISA. Total CD127 and sCD127 mRNA level was measured by real-time PCR. CD8
T cells were stimulated with recombinant human IL-7, along with signaling pathway inhibitors. CD8
T cells were co-cultured with melanoma cell line, and the cytotoxicity of CD8
T cells was assessed by measurement of lactate dehydrogenase expression.
Plasma sCD127 was lower in melanoma patients compared with controls. The percentage of CD8
T cells expressing mCD127 was higher, while sCD127 mRNA level was lower in peripheral and tumor-infiltrating CD8
T cells from melanoma patients. There was no significant difference of total CD127 mRNA expression in CD8
T cells between groups. IL-7 stimulation enhanced total CD127 and sCD127 mRNA expression and sCD127 release by CD8
T cells. However, mCD127 mRNA expression on CD8
T cells was not affected. This process was mainly mediated by phosphatidylinositol 3-kinase (PI3K) pathway. CD8
T cells from melanoma patients exhibited decreased cytotoxicity. IL-7 stimulation promoted CD8
T cell cytotoxicity, while inhibition of PI3K dampened IL-7-induced elevation of CD8
T cell cytotoxicity.
The current data suggested that insufficient IL-7 secretion might contribute to CD8
T cell exhaustion and CD127 dysregulation in patients with primary cutaneous melanoma. |
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ISSN: | 1471-2172 1471-2172 |
DOI: | 10.1186/s12865-022-00509-0 |