High sensitivity of cancer exome-based CD8 T cell neo-antigen identification
نویسندگان
چکیده
Recent data suggest that T-cell reactivity against tumor-specific neo-antigens may be central to the clinical efficacy of cancer immunotherapy. The development of personalized vaccines designed to boost T-cell reactivity against patient specific neo-antigens has been proposed largely on the basis of these findings. Work from several groups has demonstrated that novel tumor-specific antigens can be discovered through the use of cancer exome sequencing data, thereby providing a potential pipeline for the development of patient-specific vaccines. Importantly though, it has not been established which fraction of cancer neo-antigens that can be recognized by CD8+ T cells is successfully uncovered with the current exome-based epitope prediction strategies. Here, we use a data set comprising human cancer neo-antigens that was previously identified through the use of unbiased, computational-independent strategies to describe the potential of cancer exome-based neo-antigen discovery. This analysis shows a high sensitivity of exome-guided neo-antigen prediction of approximately 70%. We propose that future research should focus on the analysis and optimization of the specificity of neo-antigen prediction, and should undoubtedly entail the clinical evaluation of patient-specific vaccines with the aim of inducing immunoreactivity against tumor-displayed neo-antigens in a physiologically relevant context.
منابع مشابه
New approaches in cancer immunotherapy: review article
Cancer immunotherapy refers to any intervention that leverages the immune system to eliminate a malignancy. Successful cancer immunotherapies generate an anti-cancer response that is systemic, specific, and durable and overcome to the primary limitations of traditional cancer treatment modalities. In this review paper, the effective methods in immune system to treat cancer, such as immunosuppre...
متن کاملTetramer based approach for efficient identification and isolation of neo-antigen specific CD8 T cells from peripheral blood (PBL) of patients with metastatic cancers
Methods The strategy utilized whole exome sequencing data to identify somatic non-synonymous mutations and then insilico algorithms to predict minimal epitopes encoding mutated amino acids for each patient specific HLA-allele. CD8-enriched PBL from each patient were stained with tetramers generated in house by a UV-exchangeable technique as previously described for A*02:01, A*03:01, A*11:01, B*...
متن کاملCCD107a Expression and IFN-γ Production as Markers for Evaluation of Cytotoxic CD3+ CD8+ T Cell Response to CMV Antigen in Women with Recurrent Spontaneous Abortion
متن کامل
Cytotoxic T-Cell Markers and Cytokines in Human Papillomavirus 16
Background and Aim: Cervical cancer is the fourth main cause of mortality among women, and annually about half a million new cases are detected in developed countries. Based on oncological studies, human papillomavirus (HPV) is classified into two categories: high-risk type and low-risk type, and most cases are related to the high-risk type of human papillomavirus. HPV 16 and 18 are among the m...
متن کاملDeciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity
The precise identification of Human Leukocyte Antigen class I (HLA-I) binding motifs plays a central role in our ability to understand and predict (neo-)antigen presentation in infectious diseases and cancer. Here, by exploiting co-occurrence of HLA-I alleles across ten newly generated as well as forty public HLA peptidomics datasets comprising more than 115,000 unique peptides, we show that we...
متن کامل