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  • Combined effect of anti-BAG3 and anti-PD-1 treatment on macrophage infiltrate, CD8+ T cell number and tumour growth in pancreatic cancer

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Combined effect of anti-BAG3 and anti-PD-1 treatment on macrophage infiltrate, CD8+ T cell number and tumour growth in pancreatic cancer
  1. Vittoria Iorio1,2,
  2. Alessandra Rosati1,2,
  3. Raffaella D’Auria1,2,
  4. Margot De Marco1,2,
  5. Liberato Marzullo1,2,
  6. Anna Basile1,2,
  7. Michelina Festa1,3,
  8. Maria Pascale1,3,
  9. Paolo Remondelli2,
  10. Mario Capunzo2,
  11. Gianluca Sala4,
  12. Verena Damiani4,
  13. Giuseppina Amodio2,
  14. Marta Di Nicola4,
  15. Rossano Lattanzio4,
  16. Maria Caterina Turco1,2,
  17. Vincenzo De Laurenzi1,4
  1. 1 Biouniversa srl, c/o University of Salerno, Montoro, Avellino, Italy
  2. 2 Department of Medicine, Surgery and Dentistry, Schola Medica Salernitana, University of Salerno, Baronissi, Salerno, Italy
  3. 3 Department of Pharmacy, Division of Biomedicine ‘A Leone’, University of Salerno, Fisciano, Salerno, Italy
  4. 4 Department of Medicine and Biotechnology, University G d’Annunzio and CeSI-MeT, Chieti, Italy
  1. Correspondence to Professor Maria Caterina Turco, Department of Medicine and Surgery, Schola Medica Salernitana, University of Salerno, Baronissi, Salerno 84081, Italy; mcturco{at}unisa.it

https://doi.org/10.1136/gutjnl-2017-314225

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    We read with great interest the article by Zhang et al 1 showing that CD8+ cell infiltration in pancreatic tumours can be enhanced by depletion of myeloid cells (CD11b+ macrophages and myeloid-derived suppressor cells) and that the depletion of CD11b+ cells resulted in decreased PD-L1 expression on cancer cells thus impairing the triggering of the inhibitory receptor PD-1 on T cells.1 Recruitment and activation of CD8+ lymphocytes in tumours are suppressed by mechanisms only partially understood and rescuing CD8+ cell infiltrate in tumours is one of the objectives of immunotherapies.1 2 Tumour-associated macrophages (TAMs) play a crucial role in the relation between tumour cells and their environment.3 Here, we confirm the interplay between macrophages and CD8+ cells in pancreatic cancer and identify a potential way to exploit this enhancing effect of anti-PD-1 treatment. Indeed, we show that reduction of macrophage infiltrate, through treatment with an anti-Bcl-2-Associated athanoGene 3 (BAG3) antibody,4 results in increased number of CD8+ cells in pancreatic tumours in a murine model. BAG3 is a co-chaperone of …

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