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Concerted BAG3 and SIRPα blockade impairs pancreatic tumor growth.
De Marco, Margot; Gauttier, Vanessa; Pengam, Sabrina; Mary, Caroline; Ranieri, Bianca; Basile, Anna; Festa, Michela; Falco, Antonia; Reppucci, Francesca; Cammarota, Anna Lisa; Acernese, Fausto; De Laurenzi, Vincenzo; Sala, Gianluca; Brongo, Sergio; Miyasaka, Masayuki; Shalapour, Shabnam; Vanhove, Bernard; Poirier, Nicolas; Iaccarino, Roberta; Karin, Michael; Turco, Maria Caterina; Rosati, Alessandra; Marzullo, Liberato.
Afiliación
  • De Marco M; Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
  • Gauttier V; BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
  • Pengam S; OSE Immunotherapeutics, Nantes, France.
  • Mary C; OSE Immunotherapeutics, Nantes, France.
  • Ranieri B; OSE Immunotherapeutics, Nantes, France.
  • Basile A; Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
  • Festa M; Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
  • Falco A; BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
  • Reppucci F; BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
  • Cammarota AL; Department of Pharmacy, University of Salerno, Fisciano, SA, 84084, Italy.
  • Acernese F; Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
  • De Laurenzi V; BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
  • Sala G; Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
  • Brongo S; Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
  • Miyasaka M; Department of Pharmacy, University of Salerno, Fisciano, SA, 84084, Italy.
  • Shalapour S; BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
  • Vanhove B; Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy.
  • Poirier N; Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy.
  • Iaccarino R; Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
  • Karin M; Immunology Frontier Research Center, Osaka University, Yamada-oka, Suita, Japan.
  • Turco MC; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.
  • Rosati A; OSE Immunotherapeutics, Nantes, France.
  • Marzullo L; OSE Immunotherapeutics, Nantes, France.
Cell Death Discov ; 8(1): 94, 2022 Mar 03.
Article en En | MEDLINE | ID: mdl-35241649
ABSTRACT
The BAG3- and SIRPα- mediated pathways trigger distinct cellular targets and signaling mechanisms in pancreatic cancer microenvironment. To explore their functional connection, we investigated the effects of their combined blockade on cancer growth in orthotopic allografts of pancreatic cancer mt4-2D cells in immunocompetent mice. The anti-BAG3 + anti-SIRPα mAbs treatment inhibited (p = 0.007) tumor growth by about the 70%; also the number of metastatic lesions was decreased, mostly by the effect of the anti-BAG3 mAb. Fibrosis and the expression of the CAF activation marker α-SMA were reduced by about the 30% in animals treated with anti-BAG3 mAb compared to untreated animals, and appeared unaffected by treatment with the anti-SIRPα mAb alone; however, the addition of anti-SIRPα to anti-BAG3 mAb in the combined treatment resulted in a > 60% (p < 0.0001) reduction of the fibrotic area and a 70% (p < 0.0001) inhibition of CAF α-SMA positivity. Dendritic cells (DCs) and CD8+ lymphocytes, hardly detectable in the tumors of untreated animals, were modestly increased by single treatments, while were much more clearly observable (p < 0.0001) in the tumors of the animals subjected to the combined treatment. The effects of BAG3 and SIRPα blockade do not simply reflect the sum of the effects of the single blockades, indicating that the two pathways are connected by regulatory interactions and suggesting, as a proof of principle, the potential therapeutic efficacy of a combined BAG3 and SIRPα blockade in pancreatic cancer.

Texto completo: 1 Colección: 01-internacional Idioma: En Revista: Cell Death Discov Año: 2022 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Idioma: En Revista: Cell Death Discov Año: 2022 Tipo del documento: Article País de afiliación: Italia