Our in vitro macrophage-based assays are relevant to assess immunotherapeutics and question their mechanisms of action.
Conversing with Professor Antoine Italiano, a worldwide expert on early drug development, phase I oncology trials and immuno-oncology, upon the release of a recent article in Clinical Cancer Research.
Over the past four years, Explicyte and Bergonié Institute have been conducting joint translational research programs. Among these efforts, Explicyte and a research team led by Pr. Italiano at Bergonié Institute identified a key biomarker predictive of the efficacy of immunotherapy in oncology.
ASCO Annual Meeting ended last week! Back in France, our CEO, Alban Bessede shares with us his observations and thoughts on this year’s edition.
Discover our latest publication, titled Standardized Pathology Screening of Mature Tertiary Lymphoid Structures in Cancers.
In the context of cancer immune surveillance, dendritic cells (DCs) are key immune cells as they possess a unique ability to prime and expand antigen-specific CD4 and CD8 T cells. While trafficking from the tumor to the draining lymph nodes, they can cross-present tumor antigens and initiate a specific anti-tumor immune response. Even though several subsets exist, DCs must receive an activating signal to initiate a process of maturation that converts them from an accumulation to an antigen presentation mode to finally promote immunity or tolerance depending on the nature of the stimulus.
Thus, considering the importance of DCs in fine-tuning T cell response, their manipulation represents an attractive approach to elicit or boost an anti-tumor immune response. For this purpose, benefiting from a robust assay that evaluates the function and immunomodulation of DCs is highly valuable.
To this end, we have developed and validated a mixed leukocyte reaction (MLR) assay which is based on a co-culture of allogenic CD4+ T cells (responder) and monocyte-derived DCs (stimulator). The data shown here, originating from independent donor pairs, illustrate stimulatory or immunosuppressive properties of reference compounds. Indeed, while Adenosine, a well-known immunomodulatory nucleoside, favored a “tolerogenic” profile that translated into a limited MLR response as shown through lower levels of cytokines released in the co-culture, Nivolumab application significantly boosted the MLR response.
Hence, this dataset underlines the effectiveness of our assay in addressing the ability of test items to modulate DC-mediated immune responses.
![Figure MLR VF](https://explicyte.com/wp-content/uploads/2024/05/Figure-MLR-VF.png)
MLR in allogenic human mDC/CD4 T cell co-cultures from independent donor pairs is enhanced upon PD1 inhibition and limited by Adenosine.
Isolated peripheral blood monocyte-derived DCs are co-cultured with allogenic CD4+ T cells. At the end of the co-culture period, IFNg (A) and IL2 (B) levels released in the supernatants are measured by HTRF.
While mature DCs display T-cell stimulating ability underlined through the MLR response, this response is further optimized following PD1 blockade with Nivolumab and limited upon Adenosine treatment.
More about our MLR assays
Thus, considering the importance of DCs in fine-tuning T cell response, their manipulation represents an attractive approach to elicit or boost an anti-tumor immune response. For this purpose, benefiting from a robust assay that evaluates the function and immunomodulation of DCs is highly valuable.
To this end, we have developed and validated a mixed leukocyte reaction (MLR) assay which is based on a co-culture of allogenic CD4+ T cells (responder) and monocyte-derived DCs (stimulator). The data shown here, originating from independent donor pairs, illustrate stimulatory or immunosuppressive properties of reference compounds. Indeed, while Adenosine, a well-known immunomodulatory nucleoside, favored a “tolerogenic” profile that translated into a limited MLR response as shown through lower levels of cytokines released in the co-culture, Nivolumab application significantly boosted the MLR response.
Hence, this dataset underlines the effectiveness of our assay in addressing the ability of test items to modulate DC-mediated immune responses.
![Figure MLR VF](https://explicyte.com/wp-content/uploads/2024/05/Figure-MLR-VF.png)
MLR in allogenic human mDC/CD4 T cell co-cultures from independent donor pairs is enhanced upon PD1 inhibition and limited by Adenosine.
Isolated peripheral blood monocyte-derived DCs are co-cultured with allogenic CD4+ T cells. At the end of the co-culture period, IFNg (A) and IL2 (B) levels released in the supernatants are measured by HTRF.
While mature DCs display T-cell stimulating ability underlined through the MLR response, this response is further optimized following PD1 blockade with Nivolumab and limited upon Adenosine treatment.
More about our MLR assays
We are thrilled to announce that Explicyte will be attending the AACR annual meeting this year in Orlando, to share our latest developments and translational research works.
A new anti-PD1 resistant mouse sarcoma model, ovarian cancer ascites as a remarkable tool for translational research or our GeoMx platform to support your spatial transcriptomics programs... check out our best highlights of 2022!
Discover our latest publication, titled Phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced breast cancer!
Discover how to fully exploit the mixed leukocyte reaction assay for assessing immunotherapeutics on dendritic cell function and mediated immune response.
Discover our latest article, titled Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma.
We very much look forward to attending the @Society for Immunotherapy of Cancer Annual Meeting in Boston from November 8 to 12, and to showcasing our recent research works through our posters. Plan to stop by to talk of them and about your research programs.