In vitro chemosensitivity of feline injection site-associated sarcoma cell lines to carboplatin

2017 ◽  
Vol 47 (2) ◽  
pp. 219-226 ◽  
Author(s):  
Elizabeth A. Maxwell ◽  
Heidi Phillips ◽  
David J. Schaeffer ◽  
Timothy M. Fan
2001 ◽  
Vol 62 (9) ◽  
pp. 1354-1357 ◽  
Author(s):  
Laurel E. Williams ◽  
Nilanjana Banerji ◽  
Jeffrey S. Klausner ◽  
Vivek Kapur ◽  
Sagarika Kanjilal

2002 ◽  
Vol 63 (5) ◽  
pp. 728-732 ◽  
Author(s):  
Nilanjana Banerji ◽  
Xia Li ◽  
Jeffrey S. Klausner ◽  
Vivek Kapur ◽  
Sagarika Kanjilal

2021 ◽  
Vol 12 ◽  
Author(s):  
Darina Ocadlikova ◽  
Mariangela Lecciso ◽  
Javier Martin Broto ◽  
Katia Scotlandi ◽  
Michele Cavo ◽  
...  

BackgroundHigh-grade sarcomas are a heterogeneous group of aggressive tumors arising in bone and soft tissues. After relapse, treatment options are limited. The multi-targeted receptor tyrosine kinase inhibitors (TKIs) sunitinib and inhibitor of PD-1 (anti-PD-1) nivolumab have shown antitumor activity in selected subtypes. In this study, we examine the role of TKIs and PD-1 based therapy in in vitro cocultures of sarcoma.MethodsThe human osteosarcoma (SaOS-2) and synovial sarcoma (SYO-1) cell lines were treated with sunitinib. After cell death and proliferation assessment, expression of PD-L1 was analyzed by flow cytometry. Sunitinib-treated sarcoma cells were cocultured with dendritic cells (DCs), and the phenotype of mature DCs was determined by flow cytometry. Mature DCs were cultured with autologous T cells. PD-1 expression on T cells, their proliferation, T regulatory cell (Tregs) induction and IFN-γ production, before and after nivolumab exposure, were analyzed.ResultsAlong with its anti-proliferative and direct pro-apoptotic effect on sarcoma cell lines, sunitinib prompted PD-L1 upregulation on sarcoma cells. Interestingly, sunitinib-treated sarcoma cells drive DCs to full maturation and increase their capacity to induce sarcoma-reactive T cells to produce IFN-γ. Conversely, no effect on T cell proliferation and T cell subpopulation composition was observed. Moreover, both bone and synovial sarcoma cell lines induced Tregs through DCs but sunitinib treatment completely abrogated Treg induction. Finally, sarcoma cell lines induced PD-1 upregulation on both effector T cells and Tregs when loaded into DCs, providing a rationale for using PD-1 blockade. Indeed, PD-1 blockade by nivolumab synergized with sunitinib in inducing IFN-γ-producing effector T cells.ConclusionsTaken together, our in vitro data indicate that the treatment of sarcoma cells with sunitinib can exert significant changes on immune cell subsets toward immune activation, leading to DC-based cross-priming of IFN-γ-producing effector T cells and reduced Treg induction. PD-1 blockade with nivolumab has a synergistic effect with sunitinib, supporting the use of TKI and anti-PD-1 approach in sarcomas, and perhaps in other cancers. DC-targeted drugs, including toll-like receptor 3 inhibitors and CD47 inhibitors, are under development and our preclinical model might help to better design their clinical application.


2014 ◽  
Vol 96 (2) ◽  
pp. 304-307 ◽  
Author(s):  
M. Turek ◽  
R. Gogal ◽  
C. Saba ◽  
M.L. Vandenplas ◽  
J. Hill ◽  
...  

1988 ◽  
Vol 15 (4) ◽  
pp. 937-942 ◽  
Author(s):  
Ralph R. Weichselbaum ◽  
Michael A. Beckett ◽  
Michael A. Simon ◽  
Carla McCauley ◽  
Daniel Haraf ◽  
...  

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