Probable HLA-mediated immunoediting of JAK2 V617F-driven oncogenesis

Ivanova, Milena; Tsvetkova, Gergana; Lukanov, Tsvetelin; Stoimenov, Angel; Hadjiev, Evgueniy; Shivarov, Velizar

doi:10.1016/j.exphem.2020.09.200

Cited by 8 publications

(23 citation statements)

References 69 publications

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“…We did not have our own expression data, so we sought to provide such evidence using publicly available datasets. We were able to show that bone marrow (BM)-derived CD34+ cells from PV and ET downregulated key components of antigen processing and presentation machinery, including HLA-A and HLA-B (Ivanova et al 2020). The same phenomenon was not observed in PMF and PV peripheral blood (PB) CD34+ cells.…”

Section: Using Publicly Available Omics Datasets To Build or Support ...mentioning

confidence: 84%

“…We genotyped a large number of MPN patients and healthy controls and demonstrated that two HLA class I alleles were significantly less frequent in JAK2 V617F+ patients in comparison to healthy individuals. Interestingly, we used a bioinformatic approach to show that the HLA-B*35:01 allele can bind a specific 9-mer peptide derived from the mutant JAK2 protein (NetMHCpan server) (Ivanova et al 2020). Using other bioinformatic tools, we were also able to show that the same peptide was likely to be successfully processed and presented in the HLA class I antigen processing and presentation pathway.…”

Section: Using Publicly Available Omics Datasets To Build or Support ...mentioning

confidence: 99%

“…Therefore, we proposed that adaptive immune response through cognate T cells can edit early carcinogenesis in JAK2 V617F+ MPN stem cells (MPN-SCs) in the presence of alleles such as HLA-B*35:01, which are able to present JAK2 V617F-derived peptides efficiently (Fig. 2) (Ivanova et al 2020). The major criticism of that hypothesis would be that the protection is not absolute and JAK2 V617F+ MPNs can still develop even in the presence of potentially protective HLA class I alleles.…”

Section: Using Publicly Available Omics Datasets To Build or Support ...mentioning

confidence: 99%

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Asking Existing Data the Right Questions: Data Mining as a Research Option in Low- and Middle-Income Countries

Shivarov

2022

Improving Oncology Worldwide

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This chapter was inspired by my participation in the tenth anniversary alumni meeting of the Master Online Advanced Oncology Study Program that was held online in the times of unprecedented COVID-19 pandemics in October 2020. To a large extent, the text is a personal retrospective of my research endeavors in cancer biology during the last decade. Most of the ideas that I addressed as well as the approaches used were inspired by my participation in the program. I do hope that these personal revelations will help young professional with genuine interest in cancer research having limited resources in designing and performing their own research projects.

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Section: Using Publicly Available Omics Datasets To Build or Support ...mentioning

confidence: 84%

Section: Using Publicly Available Omics Datasets To Build or Support ...mentioning

confidence: 99%

Section: Using Publicly Available Omics Datasets To Build or Support ...mentioning

confidence: 99%

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Asking Existing Data the Right Questions: Data Mining as a Research Option in Low- and Middle-Income Countries

Shivarov

2022

Improving Oncology Worldwide

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“…Loss of HLA helps cancer cells escape immunorecognition. 65 In the tumour immune microenvironment, the immune cells are essential. Among them, helper T cells (Th) include Th1, Th2, Th17, Th9 and other cell subsets.…”

Section: Discussionmentioning

confidence: 99%

IK: A novel cell mitosis regulator that contributes to carcinogenesis

Gao

Han

Bai

et al. 2021

Cell Biochemistry & Function

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Carcinogenesis is characterized by abnormal regulation of cell growth and cell death.IK is a novel cell mitosis regulator that may contribute to carcinogenesis. Previous studies showed that the loss of IK expression resulted in cell mitotic arrest and even cell death. Besides, IK can also inhibit the interferon gamma (IFN-γ)-induced expression of human leukocyte antigen (HLA) class II antigen, which is associated with tumour immune microenvironment. To gain insight into the current research progress regarding IK, we conducted a review and searched the limited literature on IK using PubMed or Web of Science. In this review, we discussed the possible biological functions and mechanisms of IK in cancer and its immune microenvironment. Future perspectives of IK were also mentioned to explore its clinical significance.

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“…Using high‐resolution mass spectrometry, such epitopes relevant to several cancers have been discovered making possible therapies based on harnessing antigen presentation by means of vaccination, as well as T cell expansion and cell therapy [ 320 , 321 , 322 , 323 , 324 , 325 , 326 , 327 ]. Some of the neoepitopes were generated from oncogenic driver mutations, not only lending to highly personalised anti‐cancer vaccination but to ‘off the shelf’ vaccines for individuals expressing HLA alleles of a supertype [ 327 , 328 , 329 , 330 ]. Neoepitopes are not only generated by snSNPs, but can emerge from frameshift mutations via dysregulated alternative splicing and exitron splicing events, and microsatellite instability, all of which are hallmarks of tumorigenesis [ 331 , 332 , 333 , 334 ].…”

Section: Taking Antigen Presentation To the Bazaarmentioning

confidence: 99%

Know thy immune self and non‐self: Proteomics informs on the expanse of self and non‐self, and how and where they arise

Joyce

Ternette

2021

Proteomics

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T cells play an important role in the adaptive immune response to a variety of infections and cancers. Initiation of a T cell mediated immune response requires antigen recognition in a process termed MHC (Major Histocompatibility Complex) restriction. A T cell antigen is a composite structure made up of a peptide fragment bound within the antigen-binding groove of an MHC-encoded class I or class II molecule. Insight into the precise composition and biology of self and non-self immunopeptidomes is essential to harness T cell mediated immunity to prevent, treat, or cure infectious diseases and cancers. T cell antigen discovery is an arduous task! The pioneering work in the early 1990s has made large-scale T cell antigen discovery possible. Thus, advancements in mass spectrometry coupled with proteomics and genomics technologies make possible T cell antigen discovery with ease, accuracy, and sensitivity. Yet we have only begun to understand the breadth and the depth of self and non-self immunopeptidomes because the molecular biology of the cell continues to surprise us with new secrets directly related to the source, and the processing and presentation of MHC ligands. Focused on MHC class I molecules, this review, therefore, provides a brief historic account of T cell antigen discovery and, against a backdrop of key advances in molecular cell biologic processes, elaborates on how proteogenomics approaches have revolutionized the field.

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Probable HLA-mediated immunoediting of JAK2 V617F-driven oncogenesis

Cited by 8 publications

References 69 publications

Asking Existing Data the Right Questions: Data Mining as a Research Option in Low- and Middle-Income Countries

Asking Existing Data the Right Questions: Data Mining as a Research Option in Low- and Middle-Income Countries

IK: A novel cell mitosis regulator that contributes to carcinogenesis

Know thy immune self and non‐self: Proteomics informs on the expanse of self and non‐self, and how and where they arise

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