Scientific communications

To pursue our commitment to expand cutting-edge transcriptomic approaches in order to identify novel biomarkers and discover novel actionable targets, our work rely on the GeoMx-DSP technology platform (NanoStringTM) and appropriate target panels – including the Cancer Transcriptome Atlas as well as the Whole Transcriptome Atlas (1800 and 18000 genes, respectively) – an approach which is increasingly reported in scientific publications.

The development of immune checkpoint blockers (ICB) has considerably changed the therapeutic armamentarium for the management of cancer. Blocking the PD-1/PD-L1 axis interaction has demonstrated remarkable anti-cancer activity and has led to approval of anti-PD-1/PD-L1 drugs in several solid tumors. However, most patients receiving PD(L)-1 blockers do not derive clinical benefit. Therefore, there is a crucial need to decipher mechanisms underlying sensitivity / resistance to cancer immunotherapies which can ultimately lead to the identification of novel therapeutic targets.

Take advantage of our upcoming shuttle session - scheduled early-December - to cost-effectively run your candidates on our robust DC differentiation and Mixed Leukocyte Reaction (MLR) assays thereby saving up to 25% on initial cost. 

Characterized through adenosine-mediated suppression results, our validated DC-based assays represent valuable tools for assessing adenosine pathway modulators as well as innovative candidate immunotherapeutics for their potential to enhance DC-mediated T cell stimulation. 

Differentiation and maturation of competent dendritic cells (DCs) is critically dependent on their microenvironment. Among factors which can, in cancer, reach high levels in the tumor microenvironment, adenosine - one of the major immunosuppressive pathways - is known to modulate the function of many cell subsets, including DCs. Adenosine receptor stimulation skews DC differentiation toward a distinct cell population which has, unlike normal myeloid DCs, tolerogenic and suppressive phenotype expressing high levels of proinflammatory and immune suppressor factors, as well as impaired allostimulatory capacity.

Fully set up and characterized syngeneic Lewis LLC1 mouse model featured by (i) a moderate tumor immune infiltration – predominantly constituted of suppressive MDSCs and (ii) accumulation of circulating MDSCs. Interestingly, we showed here that, while LLC1 tumors remain insensitive to PD1 blockade, cyclophosphamide, a reference alkylating anti-cancer agent, led to a tumor growth inhibition and survival rate improvement.

In a recent collaborative work (1) supervised by Pr A. Italiano and published in Nature Cancer (2), we highlighted that the presence of mature tertiary lymphoid structures (mTLS) – a structure of prominent B cell follicles and follicular dendritic cells adjoined to a CD4/CD8 T cell-containing zone - is a new predictive biomarker for response for immune checkpoint blockers.

In its commitment to enable drug candidate testing in a cost-saving way, Explicyte is launching an upcoming in vivo shuttle session thus providing an opportunity to speed up your cancer therapy discovery process.

Using a syngeneic MCA205 sarcoma tumor model – widely used for the evaluation of innovative cancer immunotherapies – we investigated the anti-tumor activity of several combination therapies. This model is known to be responsive to PD1/PDL1 axis blockade but only partially to anti-CTLA4 antibody. Interestingly, while an additive benefit of anti-PD1 and anti-PDL1 is observed, a clear synergistic effect is achieved upon combination of either anti-PD1 or anti-PDL1 with anti-CTLA4, with a full tumor rejection in all treated animals.

Take advantage of new available seats on board or our upcoming shuttle session, scheduled by early May, to cost-effectively run your candidates on our robust M2 macrophage polarization assaythereby saving up to 25% full cost.

Digital pathology for tumor immune infiltrate analysis and patient selection
To assess whether or not the tumor immune contexture was predictive of response to the Avelumab-Regorafenib combination regimen, Explicyte developed and ran, on baseline FFPE samples, a multiplexed immunohistofluorescence panel consisting of CD8, PD1, PDL1, CD163, IDO1, and PanKeratin markers, in addition to Dapi (Discovery XT, Roche Diagnostics).