Prognostic Value of Neoantigen Load in Immune Checkpoint Inhibitor Therapy for Cancer

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.

Keywords: biomarker; cancer; immune checkpoint inhibitor; neoantigen load; prognostic value.

Figure 1

The mechanism of tumor antigen processing, presentation on MHC class I, and improving efficacy of ICI therapy. (A) DNA mutations occurred and synthesized proteins in the tumor cells. (B) The proteins are processed into smaller peptides, displayed by major histocompatibility complex (MHC) class I molecules via APC cells, and recognized by CD8+ T effector cells as neoantigens. (C) Tumors expressing higher numbers of neoantigens are more likely to induce a significantly greater number of T cells, while tumor cells inhibit T-cell function through immune checkpoints, such as PD-L1. (D) ICI therapy blocks immune checkpoint suppression, reactivates T-cell function, and kills tumor cells. APC, antigen-presenting cell; ICI, immune checkpoint inhibitor; MHC, major histocompatibility complex; PD-L1, programmed cell death ligand 1; PD-1, programmed death receptor 1; TCR, T-cell receptors.