PMID- 35241649
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221024
IS  - 2058-7716 (Print)
IS  - 2058-7716 (Electronic)
IS  - 2058-7716 (Linking)
VI  - 8
IP  - 1
DP  - 2022 Mar 3
TI  - Concerted BAG3 and SIRPalpha blockade impairs pancreatic tumor growth.
PG  - 94
LID - 10.1038/s41420-022-00817-9 [doi]
LID - 94
AB  - The BAG3- and SIRPalpha- 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-SIRPalpha 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 alpha-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-SIRPalpha mAb alone; however, the addition of 
      anti-SIRPalpha 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 alpha-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 SIRPalpha 
      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 SIRPalpha blockade in pancreatic cancer.
CI  - (c) 2022. The Author(s).
FAU - De Marco, Margot
AU  - De Marco M
AUID- ORCID: 0000-0003-4134-1437
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
AD  - BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
FAU - Gauttier, Vanessa
AU  - Gauttier V
AD  - OSE Immunotherapeutics, Nantes, France.
FAU - Pengam, Sabrina
AU  - Pengam S
AD  - OSE Immunotherapeutics, Nantes, France.
FAU - Mary, Caroline
AU  - Mary C
AD  - OSE Immunotherapeutics, Nantes, France.
FAU - Ranieri, Bianca
AU  - Ranieri B
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
FAU - Basile, Anna
AU  - Basile A
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
AD  - BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
FAU - Festa, Michela
AU  - Festa M
AD  - BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
AD  - Department of Pharmacy, University of Salerno, Fisciano, SA, 84084, Italy.
FAU - Falco, Antonia
AU  - Falco A
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
AD  - BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
FAU - Reppucci, Francesca
AU  - Reppucci F
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
FAU - Cammarota, Anna Lisa
AU  - Cammarota AL
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
FAU - Acernese, Fausto
AU  - Acernese F
AUID- ORCID: 0000-0003-3103-3473
AD  - Department of Pharmacy, University of Salerno, Fisciano, SA, 84084, Italy.
FAU - De Laurenzi, Vincenzo
AU  - De Laurenzi V
AD  - BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
AD  - Department of Medical, Oral and Biotechnological Sciences, University "G. 
      d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy.
FAU - Sala, Gianluca
AU  - Sala G
AUID- ORCID: 0000-0002-4494-915X
AD  - Department of Medical, Oral and Biotechnological Sciences, University "G. 
      d'Annunzio" of Chieti-Pescara, 66100, Chieti, Italy.
FAU - Brongo, Sergio
AU  - Brongo S
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
FAU - Miyasaka, Masayuki
AU  - Miyasaka M
AD  - Immunology Frontier Research Center, Osaka University, Yamada-oka, Suita, Japan.
FAU - Shalapour, Shabnam
AU  - Shalapour S
AUID- ORCID: 0000-0002-4743-3706
AD  - Department of Cancer Biology, University of Texas MD Anderson Cancer Center, 
      Houston, TX, 77054, USA.
FAU - Vanhove, Bernard
AU  - Vanhove B
AD  - OSE Immunotherapeutics, Nantes, France.
FAU - Poirier, Nicolas
AU  - Poirier N
AD  - OSE Immunotherapeutics, Nantes, France.
FAU - Iaccarino, Roberta
AU  - Iaccarino R
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
FAU - Karin, Michael
AU  - Karin M
AD  - Department of Pharmacology, University of California San Diego School of 
      Medicine, La Jolla, CA, USA.
FAU - Turco, Maria Caterina
AU  - Turco MC
AUID- ORCID: 0000-0002-7835-359X
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy. mcturco@unisa.it.
AD  - BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy. mcturco@unisa.it.
FAU - Rosati, Alessandra
AU  - Rosati A
AUID- ORCID: 0000-0001-6675-0857
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
AD  - BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
FAU - Marzullo, Liberato
AU  - Marzullo L
AD  - Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", 
      University of Salerno, Baronissi, SA, 84081, Italy.
AD  - BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy.
LA  - eng
GR  - AIRC IG-18534/Fondazione Italiana per la Ricerca sul Cancro (Italian Foundation 
      for Cancer Research)/
GR  - AIRC IG-20043/Fondazione Italiana per la Ricerca sul Cancro (Italian Foundation 
      for Cancer Research)/
GR  - POR FESR Regione Campania 2014-2020/Regione Campania/
GR  - POR FESR Regione Campania 2014-2020/Regione Campania/
GR  - POR FESR Regione Campania 2014-2020/Regione Campania/
PT  - Journal Article
DEP - 20220303
PL  - United States
TA  - Cell Death Discov
JT  - Cell death discovery
JID - 101665035
PMC - PMC8894496
COIS- VG, SP, CM, BV, and NP are employees and shareholders of OSE Immunotherapeutics, 
      a biotechnology company developing SIRPalpha antagonists (NCT03990233). MDM, AB, MF, 
      AF, VDL, MCT, AR, and LM are shareholders of BIOUNIVERSA s.r.l. that provided 
      anti-BAG3 antibodies. The remaining authors declare no conflict of interest.
EDAT- 2022/03/05 06:00
MHDA- 2022/03/05 06:01
PMCR- 2022/03/03
CRDT- 2022/03/04 05:37
PHST- 2021/07/20 00:00 [received]
PHST- 2022/01/04 00:00 [accepted]
PHST- 2021/12/09 00:00 [revised]
PHST- 2022/03/04 05:37 [entrez]
PHST- 2022/03/05 06:00 [pubmed]
PHST- 2022/03/05 06:01 [medline]
PHST- 2022/03/03 00:00 [pmc-release]
AID - 10.1038/s41420-022-00817-9 [pii]
AID - 817 [pii]
AID - 10.1038/s41420-022-00817-9 [doi]
PST - epublish
SO  - Cell Death Discov. 2022 Mar 3;8(1):94. doi: 10.1038/s41420-022-00817-9.