Absence of Telomerase Leads to Immune Response and Tumor Regression in Zebrafish Melanoma - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2023

Absence of Telomerase Leads to Immune Response and Tumor Regression in Zebrafish Melanoma

Joana Nabais
Tânia Ferreira
Mounir El Maï
Malia Bird
Seniye Targen
Da Kang
Jia-Xing Yue
Tânia Carvalho
Miguel Godinho Ferreira

Résumé

Abstract Most cancers reactivate telomerase to maintain telomere length to acquire immortality. The importance of this process is well illustrated by the fact that telomerase promoter mutations are found at a high frequency in many cancer types, including melanoma. However, it is unclear when and if telomerase is strictly required during tumorigenesis. Here, we show that melanoma can occur in the absence of telomerase but is required to sustain later growth and to avoid tumor regression. We combined telomerase mutant zebrafish ( tert-/- ) with two established melanoma models and found equal melanoma incidence and invasiveness as tumors became visible. Later, however, while tert+/+ fish develop increasing larger tumors, tert-/- tumors stagnate growth and regress. tert-/- tumors showed lower cell proliferation, higher apoptosis and melanocyte differentiation. We also detected an immune response directed at tert-/- tumors. tert-/- tumors exhibited increased immune cell infiltrates and resume growth when transplanted into immunocompromised hosts. We propose that telomerase is required for melanoma in zebrafish, albeit at later stages of progression, to sustain growth while avoiding immune rejection and regression. Thus, absence of telomerase restricts melanoma through tumor-autonomous mechanisms (cell cycle arrest, apoptosis and melanocyte differentiation) and a non-tumor-autonomous mechanisms (immune rejection).

Dates et versions

hal-04288570 , version 1 (16-11-2023)

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Citer

Bruno Lopes-Bastos, Joana Nabais, Tânia Ferreira, Mounir El Maï, Malia Bird, et al.. Absence of Telomerase Leads to Immune Response and Tumor Regression in Zebrafish Melanoma. 2023. ⟨hal-04288570⟩
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