Genetic contributions of MHC class I antigen processing and presentation pathway to bladder cancer risk and recurrence

Wieczorek, Edyta; Jabłonowski, Zbigniew; Lesicka, Monika; Jabłońska, Ewa; Kutwin, Piotr; Reszka, Edyta; Garstka, Malgorzata

doi:10.4149/neo_2021_210805n1113

Cited by 6 publications

(3 citation statements)

References 39 publications

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“…Additionally, our observation of elevated macrophages in OS was consistent with previous studies (39). Similarly, using RNA-seq data, we found that a lower expression of APM-related genes, including B2M, CIITA, ERAP2, TAP2 and TAPBPL, was also associated with a shorter PFS, reflecting the increasing interest in APM biomarkers for clinical outcome and immune escape in cancer (40). Finally, RNA-seq data revealed a pattern whereby a decreased allele-specific HLA-C expression, combined with high NK cell infiltration, was linked with improved PFS.…”

Section: Discussionsupporting

confidence: 91%

The interplay between neoantigens and immune cells in sarcomas treated with checkpoint inhibition

Anzar,

Malone,

Samarakoon

et al. 2023

Front. Immunol.

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IntroductionSarcomas are comprised of diverse bone and connective tissue tumors with few effective therapeutic options for locally advanced unresectable and/or metastatic disease. Recent advances in immunotherapy, in particular immune checkpoint inhibition (ICI), have shown promising outcomes in several cancer indications. Unfortunately, ICI therapy has provided only modest clinical responses and seems moderately effective in a subset of the diverse subtypes.MethodsTo explore the immune parameters governing ICI therapy resistance or immune escape, we performed whole exome sequencing (WES) on tumors and their matched normal blood, in addition to RNA-seq from tumors of 31 sarcoma patients treated with pembrolizumab. We used advanced computational methods to investigate key immune properties, such as neoantigens and immune cell composition in the tumor microenvironment (TME).ResultsA multifactorial analysis suggested that expression of high quality neoantigens in the context of specific immune cells in the TME are key prognostic markers of progression-free survival (PFS). The presence of several types of immune cells, including T cells, B cells and macrophages, in the TME were associated with improved PFS. Importantly, we also found the presence of both CD8+ T cells and neoantigens together was associated with improved survival compared to the presence of CD8+ T cells or neoantigens alone. Interestingly, this trend was not identified with the combined presence of CD8+ T cells and TMB; suggesting that a combined CD8+ T cell and neoantigen effect on PFS was important.DiscussionThe outcome of this study may inform future trials that may lead to improved outcomes for sarcoma patients treated with ICI.

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Section: Discussionsupporting

confidence: 91%

The interplay between neoantigens and immune cells in sarcomas treated with checkpoint inhibition

Anzar,

Malone,

Samarakoon

et al. 2023

Front. Immunol.

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“…As for tapasin ( TAPBP ), it constitutes an integral component of the peptide-loading complex that allows HLA-I to present antigens on the cell surface [ 40 ]. While a reduction in TAPBP expression has been associated to tumor progression in colorectal cancer and chronic hepatitis B [ 41 , 42 ], the rs2071888 SNP has been associated with wild type gastrointestinal tumors and gallbladder cancer [ 43 , 44 ]. Furthermore, asthmatic patients carrying the CG and GG genotypes may have a higher decline in forced expiratory volume in 1 s after aspirin provocation when compared to those patients carrying the GG genotype [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic Variation and Its Clinical Relevance in a Latin American Rural Population

Olloquequi

Castro‐Santos

Díaz‐Peña

2022

IJMS

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Latin-American populations have been largely underrepresented in genomic studies of drug response and disease susceptibility. In this paper, we present a genome-wide Chilean dataset from Talca based on the Illumina Global Screening Array. This let us to compare the frequency of gene variants involved in response to drugs among our population and others, taking data from the 1000 Genomes Project. We found four single-nucleotide polymorphisms with low prevalence in Chileans when compared with African, Amerindian, East and South Asian, and European populations: rs2819742 (RYR2), rs2631367 (SLC22A5), rs1063320 (HLA-G), and rs1042522 (TP53). Moreover, two markers showed significant differences between lower and higher proportion of Mapuche ancestry groups: rs1719247 (located in an intergenic region in chromosome 15; p-value = 6.17 × 10−5, Bonferroni corrected p-value = 0.02) and rs738409 (A nonsynonymous gene variant in the PNPLA3 gene; p-value = 9.02 × 10−5, Bonferroni corrected p-value = 0.04). All of these polymorphisms have been shown to be associated with diverse pathologies, such as asthma, cancer, or chronic hepatitis B, or to be involved in a different response to drugs, such as metformin, HMG-CoA reductase inhibitors, or simvastatin. The present work provides a pharmacogenetic landscape of an understudied Latin American rural population and supports the notion that pharmacogenetic studies in admixed populations should consider ancestry for a higher accuracy of the results. Our study stresses the relevance of the pharmacogenomic research to provide guidance for a better choice of the best treatment for each individual in a population with admixed ancestry.

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“…Various studies have demonstrated that mutations or changes in the expression of TAP1 play roles in tumor immune escape and affect tumor progression, while still remain certain controversial (12)(13)(14)(15)(16)) in terms of cancer. A considerable amount of research has focused on the relationship between polymorphisms in TAP1 and tumorigenesis development (17)(18)(19).On the one hand, in some cancers, such as colorectal cancers, researchers work to promote antigen presentation and thereby enhance tumor sensitivity to drugs (20)(21)(22). The high expression of TAP1 may be associated with the production of more tumor neoantigens, which in turn initiate tumor immunity (23).…”

Section: Introductionmentioning

confidence: 99%

The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation

et al. 2022

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Transporter associated with antigen processing 1(TAP1) serves as a protein to transport antigenic peptides from the surface of the endoplasmic reticulum to the lumen of the endoplasmic reticulum when the antigens are presented by major histocompatibility complex type I (MHC-I), which has been identified to play a critical role in antigen presentation in innate immunity. In tumors, the role of TAP1 seems to remain controversial. On the one hand, given the role of TAP1 in antigen presentation, it is indicated that high TAP1 expression corresponds to the emergence of more neoantigens epitopes that facilitate the recognition for phagocytes, T cells and other cells. On the other hand, the genetic ablation of transporter associated with antigen processing (TAP) results in the presentation of new class I-restricted epitopes encoded in house-keeping products. Opposite result has been revealed by studies in other tumors suggest, which implies a more complex function of TAP1. Therefore, it’s significant to clarify the role of TAP1 in clear cell renal cell carcinoma (ccRCC). In this study, we found the elevated expression levels in mRNA and protein of TAP1 in ccRCC tissues, which indicated a relatively worse prognosis. Transwell assay and Scratch assay in vitro demonstrated the promotive role of TAP1 in ccRCC migration as well as a significant role in metastasis. And the increased expression of TAP1 resulted in more immune cells infiltrated in cancer tissues. TAP1 was also demonstrated to be related to immune regulator genes, as gene set enrichment analysis (GSEA) indicated its significant role in immune regulation. The results of CancerSEA indicated the positive association of the high-level TAP1 expression with epithelial–mesenchymal transition (EMT) and the inverse association with Cell Cycle. The effective drugs were also predicted based on TAP1 expression, of which the high level was indeed associated with resistance to multiple drugs, but some effective drugs still identified based on high TAP1 expression. According to the analysis of various databases, the role of TAP1 in ccRCC was explored, especially in relationship of TAP1 with tumor microenvironment. These results indicate that TAP1 can serve as a potential target for treatment of ccRCC.

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Genetic contributions of MHC class I antigen processing and presentation pathway to bladder cancer risk and recurrence

Cited by 6 publications

References 39 publications

The interplay between neoantigens and immune cells in sarcomas treated with checkpoint inhibition

The interplay between neoantigens and immune cells in sarcomas treated with checkpoint inhibition

Pharmacogenetic Variation and Its Clinical Relevance in a Latin American Rural Population

The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation

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