scholarly journals Dissecting the immunosuppressive tumor microenvironments in Glioblastoma-on-a-Chip for optimized PD-1 immunotherapy

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Xin Cui ◽  
Chao Ma ◽  
Varshini Vasudevaraja ◽  
Jonathan Serrano ◽  
Jie Tong ◽  
...  

Programmed cell death protein-1 (PD-1) checkpoint immunotherapy efficacy remains unpredictable in glioblastoma (GBM) patients due to the genetic heterogeneity and immunosuppressive tumor microenvironments. Here, we report a microfluidics-based, patient-specific ‘GBM-on-a-Chip’ microphysiological system to dissect the heterogeneity of immunosuppressive tumor microenvironments and optimize anti-PD-1 immunotherapy for different GBM subtypes. Our clinical and experimental analyses demonstrated that molecularly distinct GBM subtypes have distinct epigenetic and immune signatures that may lead to different immunosuppressive mechanisms. The real-time analysis in GBM-on-a-Chip showed that mesenchymal GBM niche attracted low number of allogeneic CD154+CD8+ T-cells but abundant CD163+ tumor-associated macrophages (TAMs), and expressed elevated PD-1/PD-L1 immune checkpoints and TGF-β1, IL-10, and CSF-1 cytokines compared to proneural GBM. To enhance PD-1 inhibitor nivolumab efficacy, we co-administered a CSF-1R inhibitor BLZ945 to ablate CD163+ M2-TAMs and strengthened CD154+CD8+ T-cell functionality and GBM apoptosis on-chip. Our ex vivo patient-specific GBM-on-a-Chip provides an avenue for a personalized screening of immunotherapies for GBM patients.

Author(s):  
Zheng Shi ◽  
Alan Burns ◽  
Leandro Soares Indrusiak

In this paper, the authors discuss a real-time on-chip communication service with a priority-based wormhole switching policy. The authors present a novel off-line schedulability analysis approach, worst case network latency analysis. By evaluating diverse inter-relationships and service attributes among the traffic flows, this approach can predict the packet network latency for all practical situations. The simulation results provide evidence that communication latency calculated using the real time analysis approach is safe, closely matching the figures obtained from simulation.


2015 ◽  
Vol 208 ◽  
pp. S10 ◽  
Author(s):  
Isabelle Fournier ◽  
Benoit Fatou ◽  
Maxence Wisztorski ◽  
Cristian Focsa ◽  
Michael Ziskind ◽  
...  

2015 ◽  
Vol 87 (13) ◽  
pp. 6535-6543 ◽  
Author(s):  
Alessandro Zambon ◽  
Alice Zoso ◽  
Onelia Gagliano ◽  
Enrico Magrofuoco ◽  
Gian Paolo Fadini ◽  
...  

Author(s):  
R.P. Goehner ◽  
W.T. Hatfield ◽  
Prakash Rao

Computer programs are now available in various laboratories for the indexing and simulation of transmission electron diffraction patterns. Although these programs address themselves to the solution of various aspects of the indexing and simulation process, the ultimate goal is to perform real time diffraction pattern analysis directly off of the imaging screen of the transmission electron microscope. The program to be described in this paper represents one step prior to real time analysis. It involves the combination of two programs, described in an earlier paper(l), into a single program for use on an interactive basis with a minicomputer. In our case, the minicomputer is an INTERDATA 70 equipped with a Tektronix 4010-1 graphical display terminal and hard copy unit.A simplified flow diagram of the combined program, written in Fortran IV, is shown in Figure 1. It consists of two programs INDEX and TEDP which index and simulate electron diffraction patterns respectively. The user has the option of choosing either the indexing or simulating aspects of the combined program.


2020 ◽  
Vol 67 (4) ◽  
pp. 1197-1205 ◽  
Author(s):  
Yuki Totani ◽  
Susumu Kotani ◽  
Kei Odai ◽  
Etsuro Ito ◽  
Manabu Sakakibara

2021 ◽  
Vol 2021 (4) ◽  
pp. 7-16
Author(s):  
Sivaraman Eswaran ◽  
Aruna Srinivasan ◽  
Prasad Honnavalli

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