TCLP: an online cancer cell line catalogue integrating HLA type, predicted neo-epitopes, virus and gene expression

Scholtalbers, Jelle; Boegel, Sebastian; Bukur, Thomas; Byl, Marius; Goerges, Sebastian; Sorn, Patrick; Löewer, Martin; Şahin, Uğur; Castle, John C.

doi:10.1186/s13073-015-0240-5

Cited by 69 publications

(61 citation statements)

References 27 publications

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“…Additionally, immunogenic mutations are associated with favorable patient survival (1,37). Our detection here of predicted mutant antigens (19) and immunogenic endogenous antigens after exposure to NE and P3, and the presence of endogenous antigen/HLA-A2–specific CTL in lung cancer patients, supports previous findings that neoantigen presentation may account for some of the benefits that have been observed in some patients who receive immune-checkpoint blockade (1), which enables T-cell activation in the presence of stimulating peptide/HLA class I complexes.…”

Section: Discussionsupporting

confidence: 89%

“…Additionally, a slight enrichment of mutant neoantigens was observed after NE or P3 exposure (Supplementary Fig. S3) (19). Thus, NE and P3 had the greatest impact on the lung cancer immunopeptidome by increasing low-abundance, endogenous peptides, with “low” indicating 25 or fewer events detected by MS.…”

Section: Resultsmentioning

confidence: 99%

“…For mutant peptide identification, a lookup table was generated from reported mutations with predicted binding to endogenous HLA molecules (19,20). Briefly, reported missense mutations encoded within a peptide predicted to bind endogenous HLA class I alleles were accessed from the TRON cell line portal to create a lookup table for mutant peptides for mass spectrometry discovery.…”

Section: Methodsmentioning

confidence: 99%

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Serine Proteases Enhance Immunogenic Antigen Presentation on Lung Cancer Cells

Peters

Tripathi

Kerros

et al. 2017

Cancer Immunology Research

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Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3. Additionally, NE and P3 enhanced the expression of human leukocyte antigen (HLA) class I molecules on lung cancer cells and induced unique, endogenous peptides in the immunopeptidome, as detected with mass spectrometry sequencing. Lung cancer patient tissues with high intratumoral TAM were enriched for MHC class I genes and T-cell markers, and patients with high TAM and cytotoxic T lymphocyte (CTL) infiltration had improved overall survival. We confirmed the immunogenicity of unique, endogenous peptides with cytotoxicity assays against lung cancer cell lines, using CTL from healthy donors that had been expanded against select peptides. Finally, CTL specific for serine proteases–induced endogenous peptides were detected in lung cancer patients using peptide/HLA-A2 tetramers and were elevated in tumor-infiltrating lymphocytes. Thus, serine proteases in the tumor microenvironment of lung cancers promote the presentation of HLA class I immunogenic peptides that are expressed by lung cancer cells, thereby increasing the antigen repertoire that can be targeted in lung cancer.

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Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Serine Proteases Enhance Immunogenic Antigen Presentation on Lung Cancer Cells

Peters

Tripathi

Kerros

et al. 2017

Cancer Immunology Research

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“…Similar to NK‐92 cells, exposure of GM‐YTS cells (DGE/TCR and DGEZ/TCR) to both Tyr 368‐377 loaded T2 cells and A375(Tyr) cells triggered strong antigen‐specific degranulation (). Finally, in order to confirm the selectivity of the TCR‐NK cell lines against endogenously presented target epitopes, a set of cell lines with different characteristics with regards to tyrosinase and HLA‐A2 expression were used as targets against (Fig. D).…”

Section: Resultsmentioning

confidence: 99%

“…S7). Finally, in order to confirm the selectivity of the TCR-NK cell lines against endogenously presented target epitopes, a set of cell lines with different characteristics with regards to tyrosinase and HLA-A2 expression [24] were used as targets against (Fig. 3D).…”

Section: Tcr-pmhc-mediated Antigen-specific Triggering Of Nk Cell Effmentioning

confidence: 99%

Engineering antigen‐specific NK cell lines against the melanoma‐associated antigen tyrosinase via TCR gene transfer

et al. 2019

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Introduction of Chimeric Antigen Receptors to NK cells has so far been the main practical method for targeting NK cells to specific surface antigens. In contrast, T cell receptor (TCR) gene delivery can supply large populations of cytotoxic T‐lymphocytes (CTL) targeted against intracellular antigens. However, a major barrier in the development of safe CTL‐TCR therapies exists, wherein the mispairing of endogenous and genetically transferred TCR subunits leads to formation of TCRs with off‐target specificity. To overcome this and enable specific intracellular antigen targeting, we have tested the use of NK cells for TCR gene transfer to human cells. Our results show that ectopic expression of TCR α/β chains, along with CD3 subunits, enables the functional expression of an antigen‐specific TCR complex on NK cell lines NK‐92 and YTS, demonstrated by using a TCR against the HLA‐A2‐restricted tyrosinase‐derived melanoma epitope, Tyr368‐377. Most importantly, the introduction of a TCR complex to NK cell lines enables MHC‐restricted, antigen‐specific killing of tumor cells both in vitro and in vivo. Targeting of NK cells via TCR gene delivery stands out as a novel tool in the field of adoptive immunotherapy which can also overcome the major hurdle of “mispairing” in TCR gene therapy.

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Extracellular vesicle‐packaged lncRNA from cancer‐associated fibroblasts promotes immune evasion by downregulating HLA‐A in pancreatic cancer

Yao,

Huang,

Zou

et al. 2024

J of Extracellular Vesicle

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Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune evasion that contribute to poor prognosis. Cancer‐associated fibroblasts (CAFs) play a pivotal role in orchestrating the PDAC tumour microenvironment. We investigated the role of CAF‐derived extracellular vesicle (EV)‐packaged long non‐coding RNAs (lncRNAs) in immune evasion and explored gene therapy using engineered EVs loading small interfering RNAs (siRNAs) as a potential therapeutic strategy. Our findings highlight the significance of EV‐packaged lncRNA RP11‐161H23.5 from CAF in promoting PDAC immune evasion by downregulating HLA‐A expression, a key component of antigen presentation. Mechanistically, RP11‐161H23.5 forms a complex with CNOT4, a subunit of the mRNA deadenylase CCR4‐NOT complex, enhancing the degradation of HLA‐A mRNA by shortening its poly(A) tail. This immune evasion mechanism compromises the anti‐tumour immune response. To combat this, we propose an innovative approach utilising engineered EVs as natural and biocompatible nanocarriers for siRNA‐based gene therapy and this strategy holds promise for enhancing the effectiveness of immunotherapy in PDAC. Overall, our study sheds light on the critical role of CAF‐derived EV‐packaged lncRNA RP11‐161H23.5/CNOT4/HLA‐A axis in PDAC immune evasion and presents a novel avenue for therapeutic intervention.

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TCLP: an online cancer cell line catalogue integrating HLA type, predicted neo-epitopes, virus and gene expression

Cited by 69 publications

References 27 publications

Serine Proteases Enhance Immunogenic Antigen Presentation on Lung Cancer Cells

Serine Proteases Enhance Immunogenic Antigen Presentation on Lung Cancer Cells

Engineering antigen‐specific NK cell lines against the melanoma‐associated antigen tyrosinase via TCR gene transfer

Extracellular vesicle‐packaged lncRNA from cancer‐associated fibroblasts promotes immune evasion by downregulating HLA‐A in pancreatic cancer

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