Bordeaux, France — June 12, 2023 — Over the past four years, Explicyte and Bergonié Institute have been conducting joint translational research programs to identify the determinants of cancer patients’ response to immunotherapy.
While immunotherapy has become a major therapeutic breakthrough across several cancer indications, response rates remain limited in many patients. This highlights the need to better understand the mechanisms associated with sensitivity and resistance to immune checkpoint inhibitors, and to identify predictive biomarkers that can support more personalized treatment strategies.
Identifying Biomarkers of Response to PD-1 / PD-L1 Blockade
One major research axis of the partnership focused on immune checkpoint inhibitors targeting the PD-1 / PD-L1 pathway, a key regulator of anti-tumor immune responses.
Through this collaborative work, Explicyte, a CRO specializing in immuno-oncology, and the research team led by Pr Antoine Italiano at Bergonié Institute identified mature tertiary lymphoid structures, or mTLS, as a key biomarker predictive of immunotherapy efficacy in oncology.
These findings were reported in two major publications in Nature Cancer in 2021 and Nature Medicine in 2022, supporting the ambition of making precision immunotherapy a clinical reality.
Mature TLS as Predictive Biomarkers of Immunotherapy Efficacy
In a first pioneering study, published in Nature Cancer, the team demonstrated that the presence of mature tertiary lymphoid structures within the tumor was associated with improved objective response rate, progression-free survival, and overall survival in several tumor types.
In this work, samples from three independent cohorts of cancer patients treated with PD-1 / PD-L1 axis blockers were investigated by pathologists from Bergonié Institute, relying on Explicyte’s expertise and advanced technological platforms.
These results provided a strong rationale to design the first biomarker-driven clinical trial evaluating the benefit of pembrolizumab, a monoclonal antibody targeting PD-1, in patients with sarcomas characterized by the presence of TLS.
This second study, published in Nature Medicine, demonstrated a clear benefit of immunotherapy in this selected subgroup of patients, whereas no benefit had previously been observed in unselected sarcoma patients.
Exploring Mechanisms of Resistance in TLS-Positive Patients
Beyond the identification of mature TLS as predictive biomarkers, Explicyte scientists have further contributed to the characterization of mechanisms that may limit immunotherapy efficacy in TLS-positive patients.
These investigations identified regulatory T cells, or Tregs, as an immunosuppressive cell population that may limit the efficacy of immunotherapy in patients whose tumors harbor TLS.
This work provides additional insight into the complexity of the tumor immune microenvironment and supports the development of more refined biomarker-driven strategies in immuno-oncology.
Explicyte’s Translational Platform at the Core of the Partnership
Through this collaboration, Explicyte contributed its expertise in translational immuno-oncology, tissue-based biomarker analysis, digital pathology, and multiparametric profiling of the tumor microenvironment.
These capabilities supported the identification, validation, and biological characterization of biomarkers associated with response to immune checkpoint blockade.
The partnership with Bergonié Institute illustrates Explicyte’s ability to support translational research programs that connect patient-derived biological data with clinically meaningful immunotherapy strategies.
“The partnership between Bergonié Institute and Explicyte has demonstrated its ability to achieve breakthroughs in the growing field of immuno-oncology. Our joint efforts will continue to support the strong benefit of precision immunotherapy while shedding light on our translational service capabilities.”
Alban Bessede, PhD, CEO of Explicyte
“Thanks to our research programs conducted with Explicyte, we are the first to demonstrate the benefit of biomarker-driven immunotherapy for sarcoma patients and we will continue our efforts to prove the benefit of this strategy for all cancer patients. The partnership we established with Explicyte represents a force to move forward with precision immunotherapy and bring significant advances in healthcare to cancer patients.”
Antoine Italiano, MD, PhD, Head of Early Phase Trials Unit, Bergonié Institute
About Explicyte
Explicyte is a Contract Research Organization whose mission is to support the discovery and development of pioneering therapies in immuno-oncology.
Explicyte offers integrated preclinical and translational research services combining state-of-the-art in vitro and in vivo approaches with cutting-edge technologies. Its cell-based assays are used to screen novel immunotherapies and characterize their mechanisms of action.
Relying on well-characterized syngeneic mouse tumor models, Explicyte’s comprehensive in vivo platform enables the exploration of anti-tumor immune responses to innovative immunotherapies.
Explicyte’s translational services support projects from the identification to the validation of new targets and biomarkers, through extensive analyses covering both the tumor and its microenvironment.
In addition to its service activities, Explicyte continuously develops innovative in vitro and in vivo models to best serve its clients’ programs.
About Bergonié Institute
Bergonié Institute is labeled by the French National Cancer Institute as a reference center for early-phase clinical trials in oncology and as a national referral center for the diagnosis and management of patients with sarcomas.
Between 2015 and 2018, the Early Phase Clinical Trials Unit led by Pr Antoine Italiano enabled more than 3,000 patients with advanced cancer to access an early-phase clinical trial, making Bergonié Institute a European leader in therapeutic innovation.
The Early Phase Clinical Trials Unit supports industry-sponsored research in patients with all types of solid tumors and hematological cancers.