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.

Real-time glioblastoma tumor microenvironment assessment by SpiderMass for improved patient management

“…Infiltration of various population of immune cells was found to be associated to the patient outcome in colon cancer 42 , 43 , 44 and is now recognized in many cancers. 45 Nowadays, the immunoscore is obtained from excised tissues or biopsies by immunohistochemistry (IHC) using antibodies specific to the different immune cell populations. However, the immunoscore is obtained post-surgery.…”

Causal association between skin cancer and immune cells: mendelian randomization (MR) study

“…Recently investigators identified Immunoscore-IC, a powerful biomarker that predicts the effectiveness of (ICIs) in tumor patients. Immunoscore-IC quantifies the density of CD4 + T and CD8 + cells and the distance between their cells in the tumor microenvironment, distinguishes between patients with tumors that respond and those that do not respond to treatment with ICIs, and is considered a promising predictive marker of response to antimmunotherapy [ 46 , 47 ]. Mlecnik B [ 48 ] et al found that Immunoscore accurately stratified high-risk and low-risk patients and acted as a predictor of response to chemotherapy.…”

Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?

“…The immunoscore, based on the quantification of CD3 + and CD8 + T cells at the tumor center and at the invasive margin, is correlated with disease-specific recurrence and OS in both MSS and MSI CRC patients [ 58 ]. The immunoscore immune-checkpoint (IC, immunoscore-IC) is a modified version scoring CD8 + /PD-L1 + cells, that has shown to predict response to ICI in both lung and colorectal cancer patients [ 59 ]. In particular, in the AtezoTRIBE trial of first line FOLFOXIRI plus bevacizumab with or without atezolizumab in mCRC, the addition of atezolizumab showed a more relevant clinical activity in the immunoscore-IC high subgroup of proficient MMR (pMMR) CRC patients as compared with the low subgroup [ 60 ].…”