Thus, similar to MT/ret mice, vitiligo in RetCD3ε KO mice is associated with a more efficient tumor control. Interestingly, RetCD3ε KO mice with vitiligo developed less cutaneous metastases than nonvitiligo RetCD3ε KO mice. Here, we further observed that T-cell deficiency correlated with a significant increase in the occurrence of vitiligo ( Fig. We have recently shown that T cell-deficient MT/ret mice (RetCD3ε KO mice) developed cutaneous metastases smaller than those from T cell-competent mice ( 21). Of note, melanoma cells were undetectable by flow cytometry within the secondary lymphoid organs of 6-mo-old mice ( SI Appendix, Fig. Moreover, the proportions of these subpopulations were similar to those of age-matched control mice. We did not detect any significant difference. S2 and S3), the proportions of the various myeloid and lymphoid subsets recovered from the spleen and cervical lymph nodes (LNs) (LNs that drained the primary tumor and facial cutaneous metastases) of 6-mo-old MT/ret mice with or without vitiligo ( Fig. Next, we compared, by flow cytometry ( SI Appendix, Figs. As described previously ( 14), mice with vitiligo displayed less cutaneous metastases than mice without vitiligo.
Cutaneous metastases develop in nearly two-thirds of 6-mo-old mice and vitiligo in one-third ( Fig.
Most of MT/ret mice display a primary tumor at 3 mo of age ( SI Appendix, Table S1 and ref. MT/ret mice were monitored for the occurrence of primary uveal melanoma, cutaneous metastases, and vitiligo ( SI Appendix, Fig. Altogether, our data suggest that regulatory CD4 + T cells favor tumor progression, in part, by inhibiting recruitment and/or differentiation of inflammatory monocytes in the skin. Moreover, they inhibit tumor cell proliferation in vitro through a reactive oxygen species-dependent mechanism, and both their depletion and reactive oxygen species neutralization in vivo increased tumor cell dissemination.
#Pommie avrils skin
In contrast, inflammatory monocytes/dendritic cells accumulate in the skin of MT/ret mice with active vitiligo. Regulatory T-cell depletion and IL-10 neutralization led to increased occurrence of vitiligo that correlated with a decreased incidence of melanoma metastases.
Here, we find that regulatory CD4 + T cells accumulate in the skin, the spleen, and tumor-draining lymph nodes of MT/ret mice not developing vitiligo. A total of 35% of MT/ret mice develop a vitiligo, a skin depigmentation attributable to the lysis of normal melanocytes, associated with a delay in tumor progression. Then, MT/ret mice develop cutaneous metastases and, finally, distant metastases. In this model, cancer cells disseminate early but remain dormant for several weeks. The present study evaluates the impact of immune cell populations on metastatic development in a model of spontaneous melanoma.
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