Sade-Feldman et al from the Massachusetts General Hospital Cancer Center, the Broad Institute, the Dana Farber Cancer Institute and others demonstrated in the Cell paper that: 

• Single-cell RNA-seq reveals distinct CD45 + cells associated with clinical outcome 
• The balance between two CD8 + T cell states is linked with tumor regression 
• TCF7 +CD8 + T cell frequency in tumor tissue predicts response and better survival 
• Dual blockade of CD39 with different checkpoint proteins enhances immunity

​Ex vivo culture of murine-derived organotypic tumor spheroids (MDOTS) in AIM Biotech chips is able to recapitulate the immune checkpoint response.  These assays were used to validate the authors' discoveries by co-culturing the MDOTS with defined CD8+ T cell populations (CD39+/TIM3+, CD39-/TIM3- or mixed 1:1) (see figure 5D).

In vitro 3D cell culture models bridge the gap between conventional 2D cell culture and expensive in vivo animal models. Join our webinar, where we cover how to generate simple & complex 3D organ models for research, drug metabolism, and toxicity studies using the microfluidic 3D organ-on-a-chip from AIM Biotech. Register now at this link.

Update: A detailed protocol is available for the blood-brain barrier assay. Click on the button below:

Dr Amir Aref of the Dana-Farber Cancer Institute will be sharing how short-term culture of organotypic patient tumor spheroids derived from patient xenografts in AIM chips predicts in vivo response of targeted therapies at AACR 2018 on Sunday 350pm 15th April (see the full abstract & details at this link)

Researchers at the Dana-Farber Cancer Institute and MIT have developed a novel ex vivo assay (above) to profile the PD-1 blockade, making it possible to interrogate the tumor immune microenvironment, develop novel therapeutic combinations, and facilitate precision immuno-oncology efforts. The assay is detailed by Jenkins et al in “Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids“, Cancer Discovery doi: 10.1158/2159-8290.CD-17-0833
 
The ex vivo organotypic tumor spheroid culture system was utilised by Deng et al to show that CDK4/6 inhibition augments the response to PD-1 blockade. The effect was validated in multiple in vivo murine syngeneic models, thereby providing a rationale for combining CDK4/6 inhibitors and immunotherapies. The results are detailed in “CDK4/6 Inhibition Augments Anti-Tumor Immunity by Enhancing T Cell Activation”, Cancer Discovery doi: 10.1158/2159-8290.CD-17-0915

Dana-Farber Cancer Institute news release (click here)

* Update 5th Sep 2018
Follow up publication:  *3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade. Aref AR,  Campisi M, Ivanova E, Portell A, Larios D, Piel BP... Jenkins RW. Lab on a Chip, 2018, DOI: 10.1039/C8LC00322J 

The researchers demonstrated that they could recapitulate sensitivity and innate resistance to PD-1 blockade ex vivo with an assay developed on AIM chips. They were able to profile the functional response to tumor PD-1 blockade ex vivo and unveil a novel strategy to advance precision immuno-oncology. ​