Imprimer

The present study evaluates the impact of immune cell populations on metastatic development in a model of spontaneous melanoma [mice expressing the human RET oncogene under the control of the metallothionein promoter (MT/ret mice).

Blondel

 

Arnaud Pommiera,b,c, Alexandra Audemarda,b,c, Aurélie Duranda,b,c, Renée Lengagnea,b,c, Arnaud Delpouxa,b,c,
Bruno Martina,b,c, Laetitia Dougueta,b,c, Armelle Le Campiona,b,c, Masashi Katod, Marie-Françoise Avrila,b,c,
Cédric Auffraya,b,c, Bruno Lucasa,b,c,1,2, and Armelle Prévost-Blondela,b,c,1,2

a - Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104,

b- Institut National de la Santé et de la Recherche Médicale Unité 1016, and

c- Paris Descartes University, Cochin Hospital, 75014 Paris, France; and

d- Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Aichi 466-8550, Japan

The present study evaluates the impact of immune cell populations on metastatic development in a model of spontaneous melanoma [mice expressing the human RET oncogene under the control of the metallothionein promoter (MT/ret mice)]. In this model, cancer cells disseminate early but remain dormant for several weeks. Then, MT/ ret mice develop cutaneous metastases and, finally, distant metastases. 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. 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. Regulatory T-cell depletion and IL-10 neutralization led to increased occurrence of vitiligo that correlated with a decreased incidence of melanoma metastases. In contrast, inflammatory monocytes/dendritic cells accumulate in the skin of MT/ret mice with active vitiligo. 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. 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.


Equipe : Etude de la réponse immune et de sa régulation dans le mélanome. Responsables : Armelle BLONDEL - Anne CAIGNARD


 
 

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