Walking on the side of researchers striving to establish an assay for the prediction of  the response of human lung cancer patients to cancer immunotherapy, we have established a 3D microfluidic tumour microculture system that involves the seeding of LLC (Lewis Lung Cancer) syngeneic mouse tumour aggregates in the central hydrogel channel of an Aim Microfluidic Chip  and the injection of anti-PD1 or anti-PDL1 antibodies in the two  flanking side channels.

Proteomics analysis  proteomics of the untreated vs anti-PD1 treated tumour samples revealed the signature of the response to treatment (A). Metascape analysis of increased  (B) or decreased ( C) protein expression after anti-PD1 treatment revealed the biological pathways involved.

With this data we have the proof of concept to support that a similar humanized PDL1/PD1 system can be used for screening the responses of human patients to anti-human PD1 therapeutics.

This work was performed under the European funded program “Next Generation EU” Greece 2.0, https://greece20.gov.gr/en/) BioOnChip, “Development of a Bronchoscopic Biopsies-On-Chip platform for immunotherapy drug screening in non-small cell lung cancer” that aimed to explore the applicability of an innovative 3D microfluidic microculture in predicting real-time responses to PD1-blockade in NSCLC patients, that, if efficient, might have important socioeconomic impact.

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Fibroblasts are responsible for creating and maintaining the extracellular matrix that normally supports all the connective tissues. Tumors have the ability to recruit fibroblasts (Cancer Associated Fibroblasts (CAFs)) that develop a fibrotic microenvironment that supports their growth while protecting them from the immune system. This fibroblast-generated scar tissue is associated with the reduced efficiency of chemotherapies and poor outcome of treatment.

A new publication in Nature Cancer provides evidence that reducing scar tissue with the PXS-5505 small molecule inhibitor can help to treat pancreatic cancer by making it more accessible to chemotherapy treatment. PXS-5505 is an inhibitor of the lysyl oxidase family of enzymes which causes collagen to build up around tumors creating fibrotic scar tissue that acts as a barrier inhibiting the access of chemotherapy agents. The study offers exciting evidence that therapeutic strategies that involve the targeting of tumor-associated stroma can offer several benefits to the treatment of cancer including improved chemotherapy responses, reduced metastatic burden and more importantly prolonged survival.

Read the full article in Nature Cancer