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

Figure 1.

Predictive biomarkers of response and/or survival in patients receiving immune checkpoint immunotherapy. MSI: microsatellite instability, TMB: Tumor mutational burden, GES: gene expression signature, TILs: tumor-infiltrating lymphocytes, TLS: Tertiary lymphoid structures, Immunoscore-IC: digital pathology of CD8+/PD-L1+ cells, Immunoscore: digital pathology of CD3+/CD8+ cells.

Figure 2.

Immunoscore-IC assay. Duplex chromogenic immunohistochemistry on a single FFPE slide. Representative IHC staining of tumors with CD8 and PD-L1 antibodies, before (left) and after (right) digital pathology detection. Immunoscore-IC scores are generated using densities and proximities of CD8 and PD-L1 cells.

Figure 3.

Proportion of immunoscore-IC-High and Immunoscore-IC-Low (left) in metastatic colorectal cancer patients from AtezoTribe trial. Proportion (%) of patients according to MMR, TMB and immunoscore-IC status. Proportion (%) of patients relapsing in the treatment arm for each category (right).