Identification of HLA class I-restricted immunogenic neoantigens in triple negative breast cancer

Aparicio, Belén; Repáraz, David; Ruiz, Marta; Llópiz, Diana; Silva, Leyre; Vercher, Enric; Theunissen, Patrick; Tamayo, Ibón; Smerdou, Cristian; Igea, Ana; Santisteban, Marta; Gónzalez-Deza, Cristina; Lasarte, Juan José; Hervás-Stubbs, Sandra; Sarobe, Pablo

doi:10.3389/fimmu.2022.985886

Cited by 10 publications

(3 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The discovery of mutant peptides from the HLA immunopeptidome holds signi cant importance. Recent studies have begun to investigate the HLA immunopeptidome, and emerging evidence has shown successful identi cation of neoantigens in melanoma, lung cancer, glioblastoma and breast cancer [12,[39][40][41]. However, this method is still relying on genomic-proteomic identi cation and the utilization of genomic databases for the discovery of mutant peptides.…”

Section: Discussionmentioning

confidence: 99%

COSMIC-based mutation database enhances identification efficiency of HLA-I immunopeptidome

Wang,

Zhang,

Mao

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Neoantigens have emerged as a promising area of focus in tumor immunotherapy, with several established strategies aiming to enhance their identification. Human leukocyte antigen class I molecules (HLA-I), which present intracellular immunopeptides to T cells, provide an ideal source for identifying neoantigens. However, solely relying on a mutation database generated through commonly used whole exome sequencing (WES) for the identification of HLA-I immunopeptides, may result in potential neoantigens being missed due to limitations in sequencing depth and sample quality. Method: In this study, we constructed and evaluated an extended database for neoantigen identification, based on COSMIC mutation database. This study utilized mass spectrometry-based proteogenomic profiling to identify the HLA-I immunopeptidome enriched from HepG2 cell. HepG2 WES-based and the COSMIC-based mutation database were generated and utilized to identify HepG2-specific mutant immunopeptides. Result: The results demonstrated that COSMIC-based database identified 5 immunopeptides compared to only 1 mutant peptide identified by HepG2 WES-based database, indicating its effectiveness in identifying mutant immunopeptides. Furthermore, HLA-I affinity of the mutant immunopeptides was evaluated through NetMHCpan and peptide-docking modeling to validate their binding to HLA-I molecules, demonstrating the potential of mutant peptides identified by the COSMIC-based database as neoantigens. Conclusion: Utilizing the COSMIC-based mutation database is a more efficient strategy for identifying mutant peptides from HLA-I immunopeptidome without significantly increasing the false positive rate. HepG2 specific WES-based database may exclude certain mutant peptides due to WES sequencing depth or sample heterogeneity. The COSMIC-based database can effectively uncover potential neoantigens within the HLA-I immunopeptidomes.

show abstract

Section: Discussionmentioning

confidence: 99%

COSMIC-based mutation database enhances identification efficiency of HLA-I immunopeptidome

Wang,

Zhang,

Mao

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Due to the high degree of polymorphism of HLA, the research results obtained on the association between HLA and human tumors have not proven to be entirely consistent, and future studies incorporating big data analysis are required. In addition, recent studies demonstrated that HLA affects the survival rate of patients undergoing ICI therapy (135)(136)(137). These studies have suggested that HLAs could be used to improve the efficacy of individualized treatments of patients with cancer in the future.…”

Section: Future Perspectivesmentioning

confidence: 98%

Human leukocyte antigen and tumor immunotherapy (Review)

Liu

Mou²,

et al. 2023

Int J Oncol

View full text Add to dashboard Cite

Malignant tumors seriously endanger human health and life, and restrict economic development. Human leukocyte antigen (HLA) is the expression product of the human major histocompatibility complex, which, at present, is the most complex known polymorphic system. The polymorphism and expression of HLA molecules have been demonstrated to be associated with the occurrence and development of tumors. HLA molecules can regulate the proliferation of tumor cells and inhibit antitumor immunity. In the present review, the structure and function of HLA molecules, the polymorphism and expression of HLA in tumor tissue, the roles of HLA in tumor cells and tumor immunity, and the potential clinical application of HLA in tumor immunotherapy are summarized. The overall aim of the present review is to provide relevant information for the development of antitumor immunotherapies involving HLA in the clinic. Contents 1. Introduction 2. Physiological function and structure of HLA 3. HLA polymorphism and cancer 4. Function of HLA in tumor immunity 5. Clinical significance of HLA in tumor immunotherapy 6. Future perspectives

show abstract

“…Alternative approaches to overcome this include the use of blood from HLA-matched healthy donors (with a better lymphocyte availability and lacking tumor-induced immunosuppression) to perform in vitro priming assays, 55 and in vivo experiments using transgenic mice expressing the HLA alleles of interest. 56 , 57 Taken as a whole, new methodologies have been developed to identify neoAgs generated by different types of mutations, helping to characterize their immunogenicity.…”

Section: Neoantigens Originated From Mutationsmentioning

confidence: 99%

Relevance of mutation-derived neoantigens and non-classical antigens for anticancer therapies

Aparicio,

Theunissen,

Hervas-Stubbs

et al. 2024

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

Efficacy of cancer immunotherapies relies on correct recognition of tumor antigens by lymphocytes, eliciting thus functional responses capable of eliminating tumor cells. Therefore, important efforts have been carried out in antigen identification, with the aim of understanding mechanisms of response to immunotherapy and to design safer and more efficient strategies. In addition to classical tumor-associated antigens identified during the last decades, implementation of next-generation sequencing methodologies is enabling the identification of neoantigens (neoAgs) arising from mutations, leading to the development of new neoAg-directed therapies. Moreover, there are numerous non-classical tumor antigens originated from other sources and identified by new methodologies. Here, we review the relevance of neoAgs in different immunotherapies and the results obtained by applying neoAg-based strategies. In addition, the different types of non-classical tumor antigens and the best approaches for their identification are described. This will help to increase the spectrum of targetable molecules useful in cancer immunotherapies.

show abstract

Identification of HLA class I-restricted immunogenic neoantigens in triple negative breast cancer

Cited by 10 publications

References 47 publications

COSMIC-based mutation database enhances identification efficiency of HLA-I immunopeptidome

COSMIC-based mutation database enhances identification efficiency of HLA-I immunopeptidome

Human leukocyte antigen and tumor immunotherapy (Review)

Relevance of mutation-derived neoantigens and non-classical antigens for anticancer therapies

Contact Info

Product

Resources

About