Beyond Tumor Mutation Burden: Tumor Neoantigen Burden as a Biomarker for Immunotherapy and Other Types of Therapy

Abstract

Immunotherapy has significantly improved the clinical outcome of patients with cancer. However, the immune response rate varies greatly, possibly due to lack of effective biomarkers that can be used to distinguish responders from non-responders. Recently, clinical studies have associated high tumor neoantigen burden (TNB) with improved outcomes in patients treated with immunotherapy. Therefore, TNB has emerged as a biomarker for immunotherapy and other types of therapy. In the present review, the potential application of TNB as a biomarker was evaluated. The methods of neoantigen prediction were summarized and the mechanisms involved in TNB were investigated. The impact of high TNB and increased number of infiltrating immune cells on the efficacy of immunotherapy was also addressed. Finally, the future challenges of TNB were discussed.

Keywords: biomarker; immune response; immunotherapy; tumor mutation burden; tumor neoantigen burden.

Figure 1

The use of TNB in personalized immunotherapy for patients with cancer. Tumor tissues from patients with cancer were obtained for DNA sequencing and bioinformatics prediction of TNB. Subsequently, the TCR-T, CAR-T and the cancer vaccines were designed based on TNB for personalized treatment. Finally, the patients exhibited an immune response to cancer cells. In addition, high TMB in patients with cancer can produce high TNB, which will promote T cell activation and immune cell infiltration, thereby causing an immune response in these patients. It is interesting to note that chemotherapy, radiotherapy or targeted therapy can promote the release of cancer antigens in patients with high TNB, which in turn can enhance the therapeutic effects of ICI-based treatment. This type of treatment will activate T cells, increase immune infiltration and produce immune responses. TNB, tumor neoantigen burden; TCR-T, neoantigen-specific T cell receptor engineered-T cell; CAR-T, chimeric antigen receptor-T cell; ICI, immune checkpoint inhibitor.