2024 ASCO meeting abstract Explicyte
Alban Bessede, CEO of Explicyte, and Antoine Italiano, MD at the Institut Bergonié, were in Chicago in early June at the 2024 ASCO meeting to present a recent piece of research performed in partnership with 3 French Comprehensive Cancer Centers: Institut Gustave Roussy (Paris), Institut Bergonié (Bordeaux), and Institut Claudius Regaud (Toulouse).

In this phase II trial of Regorafenib (anti-VEGFR therapy) combined with avelumab (anti-PD-L1 immunotherapy) in soft-tissue sarcoma patients with cold tumors (TLS-negative), we found a positive effect of this combotherapy in terms of anti-tumor immunity mobilization and 6-month progression-free survival (PFS).

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translational research in immuno-oncology cancer immunotherapies
Over the past 5 years, our translational team released major papers in the field of cancer immunotherapy, in collaboration with French oncologists from the Institut Bergonié and Gustave Roussy Comprehensive Cancer Centers. Here are 5 key papers to highlight what we've learned:

In Clinical Cancer Research (2024): TROP2 is a biomarker of resistance to immune checkpoint inhibition in NSCLC

In patients with advanced Non-Small Cell Lung Cancer (NSCLC) treated with PD-L1 inhibitor atezolizumab, the overexpression of trophoblast cell surface antigen 2 (TROP2) is associated with poorer progression-free survival. TROP2High patients are more likely to benefit from a combination of immunotherapy and anti-TROP2 agents.

Technologies used: Plasma Proteomics, Bulk Transcriptomics, Digital Pathology (IF), Spatial Transcriptomics

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In Clinical Cancer Research (2023): IDO1 is a potential therapeutic target for NSCLC patients with inflamed tumor microenvironment and/or TLS

By analyzing NSCLC tumor samples from 891 patients treated with immune checkpoint inhibitors or chemotherapy, we evidenced that IDO1 expression was associated with a favorable clinical outcome (ORR, PFS, OS) upon ICI but not chemotherapy. We also demonstrated that IDO1 is overexpressed within inflamed tumors and noticeably in Tertiary Lymphoid Structures (TLS). These results strongly suggest that targeting the immunosuppressive IDO1 enzyme could be beneficial in patients with inflamed tumors.

Technologies used: T-cell Killing Assay, Germinal Center Reaction Assay, Bulk Transcriptomics, Digital Pathology (IHC/IF), Spatial Transcriptomics

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In Annals of Oncology (2022): Acetaminophen negatively impacts cancer immunotherapy efficacy

Metabolomic analysis of plasma samples collected before cancer patients underwent immunotherapy revealed that the presence of Acetaminophen (APAP) correlates with a limited response to immune checkpoint blockade. This negative impact was validated in two independent prospective cohorts and further strengthened by preclinical evidence, both in vitro and in vivo. Altogether, our findings suggest that the use of Acetaminophen, one of the most widely used drugs, limits cancer immunotherapy efficacy and should be taken with caution.

Technology used: Flow cytometry, Plasma Proteomics, In Vitro Assays, In Vivo Experiments

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In Nature Cancer (2021): The presence of mature TLS is a predictive biomarker of anti-PD1/PD-L1 axis  blockers efficacy in patients with advanced cancer

We analyzed the presence of Tertiary Lymphoid Structures (TLS) in tumor samples from 328 patients with solid tumors treated with anti-PD1 or anti-PD-L1 monoclonal antibodies. We found that the presence of mature TLS is predictive of improved clinical outcome (objective response, progression-free survival, overall survival).

Technology used: Digital Pathology

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In Annals of Oncology (2021): Elevated LIF level in serum is a predictive biomarker of resistance to immune checkpoint inhibition

Using Olink-based proteomics, we analyzed the plasma samples of 387 patients with advanced cancer treated with immune checkpoint inhibitors. High levels of Leukemia inhibitory factor (LIF) emerged as indicative of poor clinical outcome. The study identifies LIF as a potential target to improve the efficacy of cancer immunotherapies.

Technology used: Plasma Proteomics

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That's it for now! If you wish to get a full picture of our scientific production, please take a look here.

And if you have a translational research project in mind, let's talk about it. We'll be happy to help.

TROP2 lung cancer
New paper in Clinical Cancer Research!  The result of a joint work between Bergonié Institute, Gustave Roussy Institute and Explicyte.

Relying on precious patient samples and cutting-edge technologies, the teams involved discovered that Trophoblast cell-surface antigen 2 (TROP2), well-known as an attractive target for antibody-drug conjugate (ADC)-based therapy, is a strong predictor of resistance to immunotherapy, but not to chemotherapy, in patients with advanced lung cancer.

Pr. Antoine Italiano (Bergonié and Gustave Roussy Institutes) supervised the entire study, which follows on previous research on tertiary lymphoid structures (more here). He shares his views on this outstanding work.

Read the article here, entitled “TROP2 is associated with primary resistance to immune checkpoint inhibition in patients with advanced non-small cell lung cancer”.


Why is TROP2 getting so much attention today?

Pr. Italiano: TROP2 emerges as a pivotal player in the realm of cancer research and therapy due to its overexpression in various cancer types (breast, lung, etc.). This high expression positions TROP2 as a promising biomarker for cancer detection but also as a prime target for therapeutic intervention.

The compelling narrative surrounding TROP2 is gaining further strength with the positive results of numerous studies evaluating the safety and efficacy of ADCs specifically designed to target TROP2. Tangible results have been achieved in breast, urothelial, and non-small cell lung cancer (NSCLC). These studies validate TROP2 targeting as a robust and successful strategy in the ongoing pursuit of effective cancer therapies.

In light of these substantial findings, TROP2 emerges as a beacon of hope and a focal point for future advances in cancer diagnosis and treatment.


What is the main result of your study? Can you comment on the link between TROP2 expression and the tumor microenvironment characteristics?

Pr. Italiano: The reason for the TROP2 upregulation in cancer cells remains unclear; however, it is postulated that TROP2 plays a crucial role in regulating cell proliferation and invasion. This suggests that its overexpression could selectively drive tumor progression. Notably, preclinical data support this hypothesis, demonstrating that TROP2 overexpression stimulates tumor growth, while TROP2 knockdown inhibits it.

Moreover, preclinical findings indicated that surface expression of TROP2 in lung cancer cells could impact the functionality of cancer cell reactive T cells, leading to apoptosis of CD8+ T cells. Intrigued by these observations, we sought to investigate the influence of TROP2 expression on treatment outcomes of NSCLC patients undergoing immunotherapy.

Our analysis of large independent patient cohorts revealed an association between TROP2 overexpression, NSCLC microenvironment, and response to immune checkpoint inhibitors. Specifically, NSCLC with low TROP2 expression had the highest abundance of immune cells, including T cells, cytotoxic lymphocytes, and B cells. Conversely, high expression of TROP2 was linked to primary resistance to immune checkpoint inhibitors. To our knowledge, this study represents the first correlation between TROP2 expression levels, tumor microenvironment, and patient outcomes.


What is the impact of this research on the clinical development of TROP2 ADC candidates?

Pr. Italiano: TROP2 targeting appears to be a very promising therapeutic strategy for patients with advanced NSCLC. Compelling results from the reference study (TROPION-Lung01) Phase III trial show the effectiveness of the main TROP2 ADC (Datopotamab deruxtecan, Dato-DXd) compared to Docetaxel, the current standard of care in chemotherapy, in NSCLC patients treated with at least one prior line of therapy.

Recent data indicate that combining TROP2 targeting with PD-1/PD-L1 inhibition yields promising responses and presents no new safety signals in patients with previously untreated advanced or metastatic NSCLC lacking actionable genomic alterations.

Building on our results, we hypothesize that patients most likely to benefit from this therapeutic strategy are those with high TROP2 expression. Notably, our finding of a strong correlation between circulating levels of TROP2 and its expression by tumor cells suggests that selection of these patients can be achieved non-invasively through a simple blood test.

This groundbreaking approach not only strengthens the potential of TROP2 as a key therapeutic target, but also introduces a practical and accessible method of patient stratification, paving the way for personalized and effective treatments at the forefront of NSCLC management.


How did Explicyte contribute to this major discovery?     

Pr. Italiano: The collaboration with Explicyte teams played a pivotal role in the success of this study. Explicyte offers a unique and comprehensive immuno-oncology platform, seamlessly integrating robust analytical technologies, for groundbreaking testing of cancer immunotherapies. This includes cutting-edge capabilities in gene sequencing, spatial transcriptomics, multiplex immunofluorescence, plasma proteomics, and more.

Explicyte being installed within Bergonié Institute, this proximity allows our clinical and research teams to foster close collaborations with them. Undeniably, this proximity favors a synergistic approach to advance our understanding of cancer immunotherapies and translate these findings into meaningful clinical applications. The invaluable contributions offered by these collaborative efforts underscore the strength of our partnership in driving innovative advances in the field of immuno-oncology.


What are the remaining challenges to radically change the outcome of NSCLC?

Pr. Italiano: NSCLC poses a myriad of challenges due to its heterogeneous nature. A significant breakthrough lies in the development and validation of a platinum-free first-line regimen for patients with advanced NSCLC, free of adverse effects.

Our results present a compelling proposition in this regard. Combining TROP2 ADC with immune checkpoint inhibitors emerges as a promising strategy, while introducing a paradigm shift in how we approach the treatment of advanced NSCLC. To the extent that it eliminates platinum from the therapeutic landscape, it holds the promise of significantly improving the quality of life of patients facing this complex and demanding disease.
mixed leukocyte reaction assay
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


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
GeoMx Whole Transcriptome Atlas
The GeoMx Whole Transcriptome Atlas (WTA) empowers to explore biology accross a tissue. The human whole transcriptome (over 18,000 protein-coding human genes) is measured in each region of interest to uncover biological changes at specific locations of the tissue. 

  • Whole transcriptome coverage with probes specific to protein coding mRNA sequences

  • Compatible with common sample types such as formalin-fixed paraffin embedded (FFPE) or fresh frozen (FF) tissue and across all human tissues types

  • Superior sensitivity to detect 1000s of unique human genes in <50 μm regions

  • Robust performance across sample types including FFPE with high concordance with RNA-seq and RNAscope™

  • Map single cell RNA-seq populations to their tissue location


GeoMx Whole Transcriptome Atlas

The GeoMx Whole Transcriptome Atlas delivers the maximum amount of sensitivity and confidence in each transcript through its unique probe architecture. The WTA profiles over 18,000 protein-coding human genes based on the human gene nomenclature committee (HUGO1) database cross-referenced with available mRNA sequences in the National Center for Biotechnology’s Information (NCBI) RefSeq database.

The WTA then allows to explore pathways across the whole transcriptome in defined regions of interest.


Learn about out Digitial Spatial Profiling (DSP) services

GeoMx Cancer Transcriptome Atlas (CTA)
The Cancer Transcriptome Atlas (CTA) is designed for comprehensive profiling of the tumor biology, tumor microenvironment, and the immune response. It covers the RNA expression of over 1,800 genes simultaneously with spatial resolution in any region of interest from a single tissue section.

  • Extensive coverage of the immune response, tissue microenvironment, tumor biology, and genes from clinically relevant genes sets such as tumor inflammation

  • Spatial measurement of single cell signatures with high sensitivity and dynamic range

  • Inclusion of genes for the Tumor Inflammation Signature, PAM50 and other clinical signatures

  • Over 100 pathways to explore all aspects of cancer and tumor biology

The CTA assay is compatible with RNAscope® and antibody visualization markers. It can also be supplemented with up to 60 additional targets of interest.

Learn about out spatial transcriptomics services

Comprehensively Annotated Pathways in the CTA

Adaptive Immunity  






































Cell Function  






































Signaling Pathways
T cells B cells Apoptosis AMPK Signaling
TCR & BCR Signaling Autophagy Androgen Signaling
Cancer Antigens Cell Adhesion & Motility EGFR Signaling
MHC Class I & II Antigen Presentation Cell Cycle ERBB2 Signaling
T-cell Checkpoints Cilium Assembly Estrogen Signaling
TH1, TH2, TH9, Th17, and Treg Differentiation Differentiation FGFR Signaling
DNA Damage Repair FoxO Signaling
Innate Immunity EMT GPCR Signaling
Complement System Endocytosis Hedgehog Signaling
Dendritic Cells Epigenetic Modification HIF1 Signaling
DNA & RNA Sensing Immortality & Stemness Insulin Signaling
Glycan Sensing Ion Transport JAK-STAT Signaling
Host Defense Peptides Lysosome MAPK Signaling
Inflammasomes Oxidative Stress MET Signaling
Myeloid Inflammation Phagocytosis mTOR Signaling
Neutrophil Degranulation Proteotoxic Stress Myc
NK Activity RNA Processing NO Signaling
NLR Signaling Senescence Notch Signaling
RAGE Signaling p53 Signaling
TLR Signaling Metabolism PDGF Signaling
Amino Acid Synthesis & Transport PI3K-Akt Signaling
Immune Response Arginine & Glutamine Metabolism PPAR Signaling
Chemokine Signaling Fatty Acid Oxidation & Synthesis Purinergic Signaling
Cytotoxicity Glycolysis & Glucose Transport Retinoic Acid Signaling
IL-1, IL-2, IL-6 & IL-17 Signaling Glycosylation TGF-beta Signaling
Immune Exhaustion IDH1/2 VEGF Signaling
Interferon Response Genes Lipid Metabolism Wnt Signaling
Lymphocyte Regulation & Trafficking Mitochondrial Metabolism / TCA
NF-kB Signaling Nucleotide Synthesis Physiology & Disease
Other Interleukin Signaling Pentose Phosphate Angiotensin System
Prostaglandin Inflammation Tryptophan & Kynurenine Metabolism Circadian Clock
TNF Signaling Vitamin & Cofactor Metabolism Drug Resistance
Type I, II, & III Interferon Signaling  









Matrix Remodeling and Metastasis
Neuroendocrine Function
Prostate Cancer

Soft Tissue Sarcoma (STS) is known to be refractory to current cancer immunotherapies including the PD1 immune checkpoint inhibitor (ICI) (Toulmonde et al., 2018), thus claiming the development of novel therapeutic strategies aiming at improving the current clinical benefit.
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