Precision Medicine for NSCLC in the Era of Immunotherapy: New Biomarkers to Select the Most Suitable Treatment or the Most Suitable Patient

Abstract

In recent years, the evolution of treatments has made it possible to significantly improve the outcomes of patients with non-small cell lung cancer (NSCLC). In particular, while molecular targeted therapies are effective in specific patient sub-groups, immune checkpoint inhibitors (ICIs) have greatly influenced the outcomes of a large proportion of NSCLC patients. While nivolumab activity was initially assessed irrespective of predictive biomarkers, subsequent pivotal studies involving other PD-1/PD-L1 inhibitors in pre-treated advanced NSCLC (atezolizumab within the OAK study and pembrolizumab in the Keynote 010 study) reported the first correlations between clinical outcomes and PD-L1 expression. However, PD-L1 could not be sufficient on its own to select patients who may benefit from immunotherapy. Many studies have tried to discover more precise markers that are derived from tumor tissue or from peripheral blood. This review aims to analyze any characteristics of the immunogram that could be used as a predictive biomarker for response to ICIs. Furthermore, we describe the most important genetic alteration that might predict the activity of immunotherapy.

Subunits of ARID1 serve as novel biomarkers for the sensitivity to immune checkpoint inhibitors and prognosis of advanced non-small cell lung cancer

“…In addition, through the activation of the antigen presentation process and anticancer cellular immunity, ARID1A and ARID1B deficiencies could modulate the TIME of NSCLC and initiate a therapeutic immune reaction to tumors. In this research, we confirmed the important role of ARID1A deficiency in elevating cancerous mutability and changing tumors to exhibit an aggressive phenotype in NSCLC, which was proposed by published works (Shen et al 2018 ; Jiang et al 2020 ; Okamura et al 2020 ; Rossi et al 2020 ) on other cancer types. Additionally, our research is the first to investigate the role of ARID1B, which is another ARID1 subunit similar to ARID1A, in changing the phenotype of cancer.…”

“…As is well known, the PD-L1 expression or TMB level did not disclose satisfied efficiency in selecting patients who might benefit from immunotherapy while plasma NGS circulating-free DNA (cfDNA) analysis in NSCLC might provides new biomarkers for cancer immunotherapy (Rossi et al 2020 ). According to the previous studies, the co-mutations of TP53 and STK11 serve as an important role in modulating the TIME of NSCLC and related to the sensitivity to ICIs treatment (Skoulidis and Heymach 2019 ).…”

Subunits of ARID1 serve as novel biomarkers for the sensitivity to immune checkpoint inhibitors and prognosis of advanced non-small cell lung cancer.

“…In addition, through the activation of the antigen presentation process and anticancer cellular immunity, ARID1A and ARID1B de ciencies could modulate the TIME of NSCLC and initiate a therapeutic immune reaction to tumors. In this research, we con rmed the important role of ARID1A de ciency in elevating cancerous mutability and changing tumors to exhibit an aggressive phenotype in NSCLC, which was proposed by published works [16][17][18]26] on other cancer types. Additionally, our research is the rst to investigate the role of ARID1B, which is another ARID1 subunit similar to ARID1A, in changing the phenotype of cancer.…”

“…As is well known, the PD-L1 expression or TMB level did not disclose satis ed e ciency in selecting patients who might bene t from immunotherapy while plasma NGS circulating-free DNA (cfDNA) analysis in NSCLC might provides new biomarkers for cancer immunotherapy [26]. According to the previous studies, the co-mutations of TP53 and STK11 serve as an important role in modulating the TIME of NSCLC and related to the sensitivity to ICIs treatment [27].…”

First-Line Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Landscape and Future Progress

“…Previous studies have shown that tumors with high microsatellite instability (MSI-H) also have a higher tumor mutation burden, indicating that there is a certain correlation between them. Moreover, a series of experimental studies have confirmed that tumor infiltrating lymphocytes (TILs), neutrophil-to-lymphocyte ratio (NLR), electronic nose analysis of exhaled breath and other biomarkers can help to screen patients who can benefit from immunotherapy for NSCLC ( Tokito et al., 2016 ; de Vries et al., 2019 ; Lee and Ruppin, 2019 ; Rossi et al., 2020 ).…”