Details

Autor(en) / Beteiligte

• Ducarouge, Benjamin
• Redavid, Anna-Rita
• Victoor, Camille
• Chira, Ruxanda
• Fonseca, Aurélien
• Hervieu, Maëva
• Bergé, Roméo
• Lengrand, Justine
• Vieugué, Pauline
• Neves, David
• Goddard, Isabelle
• Richaud, Mathieu
• Laval, Pierre-Alexandre
• Rama, Nicolas
• Goldschneider, David
• Paradisi, Andrea
• Gourdin, Nicolas
• Chabaud, Sylvie
• Treilleux, Isabelle
• Gadot, Nicolas
• Ray-Coquard, Isabelle
• Depil, Stéphane
• Decaudin, Didier
• Némati, Fariba
• Marangoni, Elisabetta
• Mery-Lamarche, Eliane
• Génestie, Catherine
• Tabone-Eglinger, Séverine
• Devouassoux-Shisheboran, Mojgan
• Moore, Kathryn J
• Gibert, Benjamin
• Mehlen, Patrick
• Bernet, Agnes

Titel

Netrin-1 blockade inhibits tumor associated Myeloid-derived suppressor cells, cancer stemness and alleviates resistance to chemotherapy and immune checkpoint inhibitor

Ist Teil von

• Cell death and differentiation, 2023-10, Vol.30 (10), p.2201-2212

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Drug resistance and cancer relapse represent significant therapeutic challenges after chemotherapy or immunotherapy, and a major limiting factor for long-term cancer survival. Netrin-1 was initially identified as a neuronal navigation cue but has more recently emerged as an interesting target for cancer therapy, which is currently clinically investigated. We show here that netrin-1 is an independent prognostic marker for clinical progression of breast and ovary cancers. Cancer stem cells (CSCs)/Tumor initiating cells (TICs) are hypothesized to be involved in clinical progression, tumor relapse and resistance. We found a significant correlation between netrin-1 expression and cancer stem cell (CSC) markers levels. We also show in different mice models of resistance to chemotherapies that netrin-1 interference using a therapeutic netrin-1 blocking antibody alleviates resistance to chemotherapy and triggers an efficient delay in tumor relapse and this effect is associated with CSCs loss. We also demonstrate that netrin-1 interference limits tumor resistance to immune checkpoint inhibitor and provide evidence linking this enhanced anti-tumor efficacy to a decreased recruitment of a subtype of myeloid-derived suppressor cells (MDSCs) called polymorphonuclear (PMN)-MDSCs. We have functionally demonstrated that these immune cells promote CSCs features and, consequently, resistance to anti-cancer treatments. Together, these data support the view of both a direct and indirect contribution of netrin-1 to cancer stemness and we propose that this may lead to therapeutic opportunities by combining conventional chemotherapies and immunotherapies with netrin-1 interfering drugs.