A Combination of Biomarkers Predict Response to Immune Checkpoint Blockade Therapy in Non-Small Cell Lung Cancer

Abstract

Immune checkpoint blockade (ICB) therapy has provided clinical benefits for patients with advanced non-small-cell lung cancer (NSCLC), but the majority still do not respond. Although a few biomarkers of ICB treatment response have been developed, the predictive power of these biomarkers showed substantial variation across datasets. Therefore, predicting response to ICB therapy remains a challenge. Here, we provided a concise combinatorial strategy for predicting ICB therapy response and constructed the ICB treatment signature (ITS) in lung cancer. The prediction performance of ITS has been validated in an independent ICB treatment cohort of NSCLC, where patients with higher ITS score were significantly associated with longer progression-free survival and better response. And ITS score was more powerful than traditional biomarkers, such as TMB and PD-L1, in predicting the ICB treatment response in NSCLC. In addition, ITS scores still had predictive effects in other cancer data sets, showing strong scalability and robustness. Further research showed that a high ITS score represented comprehensive immune activation characteristics including activated immune cell infiltration, increased mutation load, and TCR diversity. In conclusion, our practice suggested that the combination of biomarkers will lead to a better prediction of ICB treatment prognosis, and the ITS score will provide NSCLC patients with better ICB treatment decisions.

TTYH3, a potential prognosis biomarker associated with immune infiltration and immunotherapy response in lung cancer

“…Recent advances in ICBs therapy like targeting programmed cell death protein 1 (PD-1) / PD-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has provided clinical bene ts for patients with lung cancer, but the majority still do not respond. Although a few biomarkers of ICB treatment response have been developed, the predictive power of these biomarkers showed substantial variation across datasets 28,29 . To evaluate immunotherapy predictive value of TTYH3, we utilized the TIDE web tool, which is a computational framework developed to evaluate potential of tumor immune escape based on the gene expression pro les of cancer samples.…”

Identification and characterization of neoantigen-reactive CD8+ T cells following checkpoint blockade therapy in a pan-cancer setting

“…However, in other studies these have also been shown to be of weak predictive value (5). Recently proposed cancer immune predictor suggests using a combination of biomarkers to better predict the response of ICB (6,7). The neoepitope load is based on predicted neoepitopes, however, with only 2-4% of these epitopes giving a T cell response, studies have tried to explore for more precise prediction strategies (8) or to validate the presence of truly immunogenic neoepitopes as a more well-suited immune predictor (9,10).…”

Cuproptosis-related molecular subtypes direct T cell exhaustion phenotypes and therapeutic strategies for patients with lung adenocarcinoma

“…Immune checkpoint blockade (ICB) therapy has revolutionized the treatment of advanced NSCLC. It has improved the overall survival of NSCLC patients, but only a few patients have benefited in the clinical setting ( Jiang et al, 2021 ). The objective response rate to PD-1 blockade (Pembrolizumab) is 19.4% for all the patients with a median overall survival of 12.0 months ( Garon et al, 2015 ).…”