Abstract
Immune checkpoint inhibitors (ICIs) have made great progress in the field of tumors and have become a promising direction of tumor treatment. With advancements in genomics and bioinformatics technology, it is possible to individually analyze the neoantigens produced by somatic mutations of each patient. Neoantigen load (NAL), a promising biomarker for predicting the efficacy of ICIs, has been extensively studied. This article reviews the research progress on NAL as a biomarker for predicting the anti-tumor effects of ICI. First, we provide a definition of NAL, and summarize the detection methods, and their relationship with tumor mutation burden. In addition, we describe the common genomic sources of NAL. Finally, we review the predictive value of NAL as a tumor prediction marker based on various clinical studies. This review focuses on the predictive ability of NAL’s ICI efficacy against tumors. In melanoma, lung cancer, and gynecological tumors, NAL can be considered a predictor of treatment efficacy. In contrast, the use of NAL for urinary system and liver tumors requires further research. When NAL alone is insufficient to predict efficacy, its combination with other indicators can improve prediction efficiency. Evaluating the response of predictive biomarkers before the treatment initiation is essential for guiding the clinical treatment of cancer. The predictive power of NAL has great potential; however, it needs to be based on more accurate sequencing platforms and technologies.
Highlights
Tumors acquire mutations as they develop and progress
A series of follow-up clinical studies have shown that higher neoantigen load (NAL) is associated with enhanced efficacy of Immune checkpoint inhibitors (ICIs) in melanoma, non-small cell lung carcinoma (NSCLC), and colorectal cancer [6, 9,10,11]
They indicated that TET1 mutation was closely associated with higher NAL, presenting a higher objective response rate, better durable clinical benefit, longer progression-free survival (PFS), and improved overall survival (OS) in patients receiving ICIs [47]
Summary
Tumors acquire mutations as they develop and progress. These mutations can encode amino acid sequences to translate different proteins, called tumor-specific antigens or neoantigens, which are immunogenic and can be recognized and eliminated by immune cells [1, 2]. A series of follow-up clinical studies have shown that higher NAL is associated with enhanced efficacy of ICIs in melanoma, non-small cell lung carcinoma (NSCLC), and colorectal cancer [6, 9,10,11]. Wu et al conducted a comprehensive analysis of patients with TET1, a DNA demethylase that regulates DNA methylation [46] They indicated that TET1 mutation was closely associated with higher NAL, presenting a higher objective response rate, better durable clinical benefit, longer progression-free survival (PFS), and improved OS in patients receiving ICIs [47]. Shukla et al investigated whether lowmutation endometrial cancer has similar prognostic factors and analyzed the data of 90 copy number-low/endometrioid and 60 copy number-high/serous-like endometrial tumors using the TCGA dataset They found that the predicted NAL was related to specific genomic changes, such as CTNNB1 mutation, MYC amplification, and PIK3CA mutation. Yang et al investigated neoantigens in hepatocellular carcinoma and concluded that OS was not associated with NAL [74]
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