Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines

Lei, Wei‐Yi; Hsiung, Shih-Chieh; Wen, Shao-Hsuan; Hsieh, Chin-Hsuan; Chen, Chien‐Lin; Wallace, Christopher Glenn; Chang, Chien‐Chung; Liao, Shuen‐Kuei

doi:10.1155/2018/8363265

Cited by 5 publications

(4 citation statements)

References 48 publications

(45 reference statements)

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“…Although the downregulation of pHLA presentation in tumor cells is well documented in many cancers, [42][43][44][45] whether HCC cells present pHLAs at sufficient levels to activate a CTL response is still under debate. [46][47][48][49] Recent studies by Dr Bertoletti's team demonstrated that HBV antigens could be presented by HCC cells despite these antigens not being detectable by IHC techniques.…”

Section: Discussionmentioning

confidence: 99%

In vivo therapeutic effects of affinity-improved-TCR engineered T-cells on HBV-related hepatocellular carcinoma

Liu

Tian

et al. 2020

J Immunother Cancer

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BackgroundIn patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), virus-specific cytotoxic T lymphocytes (CTLs) fail to eliminate HCC cells expressing HBV antigens. As the expression of viral antigen in HBV-associated HCC may decrease to allow tumor to escape immune attacks, we hypothesized that an HBV surface antigen (HBsAg)-specific affinity-improved-T-cell receptor (TCR) will enable T cells to target HCC more effectively than corresponding wild-type-TCR. We also postulated that TCR promiscuity can be exploited to efficiently capture HBV variants that can hinder CTL-based therapeutics.MethodsWe applied flexi-panning to isolate affinity-improved TCRs binding to a variant antigen, the human leukocyte antigen (HLA)-A*02:01-restricted nonapeptide HBs371-379-ILSPFLPLL, from libraries constructed with a TCR cloned using the decapeptide HBs370-379-SIVSPFIPLL. The potency and safety of the affinity-improved-TCR engineered T-cells (Ai-TCR-T) were verified with potentially cross-reactive human and HBV-variant peptides, tumor and normal cells, and xenograft mouse models.ResultsAi-TCR-T cells retained cognate HBV antigen specificity and recognized a wide range of HBV genotypic variants with improved sensitivity and cytotoxicity. Cell infusions produced complete elimination of HCC without recurrence in the xenograft mouse models. Elevated accumulation of CD8+ Ai-TCR-T cells in tumors correlated with tumor shrinkage.ConclusionThe in vitro and in vivo studies demonstrated that HBsAg-specific Ai-TCR-T cells had safety profiles similar to those of their wild-type counterparts and significantly enhanced potency. This study presents an approach to develop new therapeutic strategies for HBV-related HCC.

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Section: Discussionmentioning

confidence: 99%

In vivo therapeutic effects of affinity-improved-TCR engineered T-cells on HBV-related hepatocellular carcinoma

Liu

Tian

et al. 2020

J Immunother Cancer

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“…The evasion can occur through various mechanisms, such as oncogenic changes induced by viruses that result in phenotypic alterations in HLA-DR; the absence of a receptor on natural killer cells that interacts with different HLA molecules, and the presence of heterogeneous cell populations within tumors that generate multiple variants with different HLA phenotypes ( 14 ). These mechanisms are relatively rare in benign tumors but can be highly efficient in promoting malignancies ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

Impaired intratumoral dendritic cell function and potential predictive value of dendritic cell markers for metastasis in malignant salivary gland tumors

Gama-Cuellar,

Díaz,

Calleja

et al. 2024

Med Oral

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Background The differentiation between primary and metastatic salivary gland neoplasms (SGNs) helps in determining appropriate management strategies, including the need for additional diagnostic tests, surveillance, or aggressive treatment. The purpose of this study was to identify and quantify the immature and mature dendritic cells (DCs) in metastatic and no metastatic SGNs and determine its association with clinicopathological findings. Material and Methods Cross-sectional, observational, and descriptive study that includes 33 malignant salivary gland neoplasms [MSGN (6, 18.1% metastatic)], and 22 pleomorphic adenomas (PA), as a control group. Clinical and histopathological characteristics were obtained. Immunohistochemistry for human leukocyte antigen D-related (HLA-DR), CD1a, CD83, and Ki-67 proteins was done. Positive intra- and peritumoral DCs were counted. Results Individuals with MSGN had a lower density of intratumoral HLA-DR+ cells than those with PA ( p =0.001), Ki-67 immunostaining was significantly higher in MSGN than in PA (6% vs. 1.4%, p <0.001). Metastatic MSGN showed less intratumoral CD1a+ than non-metastatic (3.2 vs. 165.1, p =0.001). No differences in intra- and peritumoral CD83+ cells were found between benign and malignant SGN. Conclusions These results suggest that the immune-protective function of intratumoral DCs is compromised in MSGNs. DCs markers may represent useful prediction tools for metastases in salivary gland malignancies, with crucial implications in the implementation of appropriate disease management strategies.

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“…For instance, considering the human leukocyte anKgen (HLA) [48][49][50] and B2M 51,52 genes, which encode proteins crucial for anKgen presentaKon process criKcal for acKvaKng T cells and iniKaKng an immune response against tumor cells. DysregulaKon or alteraKons in the expression of these HLA genes can impact the immune system's ability to recognize and eliminate cancer cells, directly influencing the success of ICIs 49,51 . In addiKon, validated HCC immune players, CD74 53,54 (Fig.…”

Section: Detec9ng Differen9ally Expressed Isoforms In Single-cell Lon...mentioning

confidence: 99%

IFDlong: an isoform and fusion detector for accurate annotation and quantification of long-read RNA-seq data

Wang,

Li,

et al. 2024

Preprint

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Advancements in long-read transcriptome sequencing (long-RNA-seq) technology have revolutionized the study of isoform diversity. These full-length transcripts enhance the detection of various transcriptome structural variations, including novel isoforms, alternative splicing events, and fusion transcripts. By shifting the open reading frame or altering gene expressions, studies have proved that these transcript alterations can serve as crucial biomarkers for disease diagnosis and therapeutic targets. In this project, we proposed IFDlong, a bioinformatics and biostatistics tool to detect isoform and fusion transcripts using bulk or single-cell long-RNA-seq data. Specifically, the software performed gene and isoform annotation for each long-read, defined novel isoforms, quantified isoform expression by a novel expectation-maximization algorithm, and profiled the fusion transcripts. For evaluation, IFDlong pipeline achieved overall the best performance when compared with several existing tools in large-scale simulation studies. In both isoform and fusion transcript quantification, IFDlong is able to reach more than 0.8 Spearman correlation with the truth, and more than 0.9 cosine similarity when distinguishing multiple alternative splicing events. In novel isoform simulation, IFDlong can successfully balance the sensitivity (higher than 90%) and specificity (higher than 90%). Furthermore, IFDlong has proved its accuracy and robustness in diverse in-house and public datasets on healthy tissues, cell lines and multiple types of diseases. Besides bulk long-RNA-seq, IFDlong pipeline has proved its compatibility to single-cell long-RNA-seq data. This new software may hold promise for significant impact on long-read transcriptome analysis. The IFDlong software is available at https://github.com/wenjiaking/IFDlong.

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Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines

Cited by 5 publications

References 48 publications

In vivo therapeutic effects of affinity-improved-TCR engineered T-cells on HBV-related hepatocellular carcinoma

In vivo therapeutic effects of affinity-improved-TCR engineered T-cells on HBV-related hepatocellular carcinoma

Impaired intratumoral dendritic cell function and potential predictive value of dendritic cell markers for metastasis in malignant salivary gland tumors

IFDlong: an isoform and fusion detector for accurate annotation and quantification of long-read RNA-seq data

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