Tumor mutational burden and immunotherapy in gliomas

Tumor mutational burden (TMB) is an emerging biomarker for the prediction of immunotherapy success in solid tumors. Gliomas, however, do not demonstrate a correlation between TMB and immunotherapy efficacy. Here, we discuss the potential factors influencing this discordance, focusing on the impact of neoantigen immunogenicity, clonality, expression, and presentation. Tumor mutational burden (TMB) is an emerging biomarker for the prediction of immunotherapy success in solid tumors. Gliomas, however, do not demonstrate a correlation between TMB and immunotherapy efficacy. Here, we discuss the potential factors influencing this discordance, focusing on the impact of neoantigen immunogenicity, clonality, expression, and presentation. an important component of the HLA-I complex that is involved in presentation of neoantigens. the neoantigens with a greater than ten times improvement in MHC-I binding affinity and a greater than four times improvement in MHC-II binding affinity compared with their non-mutant counterpart. the components involved in the processing and presentation of antigens. a class of immunogenic antigens that are not expressed in normal human tissue (other than testes) but are often expressed on cancer cells. the neoantigens computationally identified by predicting their ability to bind with high affinity to MHC molecules. the neoantigens that are derived from the mutations that occur early in tumorigenesis and are found in most tumor cells. the MHC-I molecules in humans that are involved in antigen processing and presentation in humans. HLA gene products are divided into classes I, II, and III based on their structure and function, and HLA-I molecules are responsible for presenting endogenous peptides to CD8+ T-cells. Furthermore, the diversity of HLA-I molecules (HLA-A, HLA-B, HLA-C) influences the number of unique neoantigens that are presented, as they are all responsible for binding specific peptides. the process of accumulating an unusually high number of somatic mutations. a neoantigen that is capable of being recognized by the host immune system and eliciting an immune response. a form of treatment that activates the immune system to attack the disease. the loss of an allele at a heterozygous locus either via simple deletion of an allele or by deletion of an allele followed by the duplication of the remaining allele. the ratio of expressed neoantigens to predicted neoantigens. the tumor-specific peptides derived from somatic mutations that are absent in normal human cells. the process of elimination of certain immunogenic neoantigens, which leads to the accumulation of neoantigens that are advantageous to the tumor cells and can promote immune evasion. the neoantigens that are derived from the mutations that occur later in malignant transformation and are found in only a fraction of tumor cells. the total number of mutations found in the DNA of cancer cells.