Light on life: immunoscore immune-checkpoint, a predictor of immunotherapy response

ABSTRACT

In the last decade, a plethora of immunotherapeutic strategies have been designed to modulate the tumor immune microenvironment. In particular, immune checkpoint (IC) blockade therapies present the most promising advances made in cancer treatment in recent years. In non-small cell lung cancer (NSCLC), biomarkers predicting response to IC treatments are currently lacking. We have recently identified Immunoscore-IC, a powerful biomarker that predicts the efficiency of immune-checkpoint inhibitors (ICIs) in NSCLC patients. Immunoscore-IC is an in vitro diagnostic assay that quantifies densities of PD-L1+, CD8+ cells, and distances between CD8+ and PD-L1+ cells in the tumor microenvironment. Immunoscore-IC can classify responder vs non-responder NSCLC patients for ICIs therapy and is revealed as a promising predictive marker of response to anti-PD-1/PD-L1 immunotherapy in these patients. Immunoscore-IC has also shown a significant predictive value, superior to the currently used PD-L1 marker. In colorectal cancer (CRC), the addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab improved progression-free survival (PFS) in patients with previously untreated metastatic CRC. In the AtezoTRIBE trial, Immunoscore-IC emerged as the first biomarker with robust predictive value in stratifying pMMR metastatic CRC patients who critically benefit from checkpoint inhibitors. Thus, Immunoscore-IC could be a universal biomarker to predict response to PD-1/PD-L1 checkpoint inhibitor immunotherapy across multiple cancer indications. Therefore, cancer patient stratification (by Immunoscore-IC), based on the presence of T lymphocytes and PD-L1 potentially provides support for clinicians to guide them through combination cancer treatment decisions.

KEYWORDS:

• biomarkers
• cancer
• immune checkpoint (IC)
• immunoscore
• immunotherapy
• PD-L1
• response
• T-cells
• Tumor microenvironment (TME)

Acknowledgments

The work was supported by INSERM, LabEx Immuno-oncology, Transcan ERAnet European project, the Society for Immunotherapy of Cancer (SITC), Association pour la Recherche contre le Cancer (ARC), Site de Recherche intégrée sur le Cancer (SIRIC), CAncer Research for PErsonalized Medicine (CARPEM), La Ligue contre le Cancer, Institut National du Cancer, France (INCa), Louis Jeantet Prize foundation, Assistance publique – Hôpitaux de Paris (AP-HP), HalioDx, Veracyte, Qatar National Research Fund (QNRF) grant number NPRP11S-0121-180351, Agence Nationale de la Recherche (ANR) Grant TERMM ANR-20-CE92-0001.

Disclosure statement

JG has patents associated with immune prognostic biomarkers and immunotherapies. JG is co-founder of HalioDx Biotech Company, a Veracyte company and has part-time employment at Veracyte. Immunoscore® a registered trademark from the National Institute of Health and Medical Research licensed to Veracyte.

Additional information

Funding

The work was supported by the Institut National de la Santé et de la Recherche Médicale Transcan ERAnet European project the Society for Immunotherapy of Cancer (SITC) Association pour la Recherche contre le Cancer (ARC) CAncer Research for PErsonalized Medicine (CARPEM) Agence Nationale de la Recherche (ANR) [TERMM ANR-20-CE92-0001]; Institut National du Cancer France (INCa) Louis Jeantet Prize foundation Assistance publique – Hôpitaux de Paris (AP-HP) HalioDx Qatar National Research Fund (QNRF) [NPRP11S-0121-180351]; LabEx Immuno-oncology La Ligue contre le Cancer .