Proteomics

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Presentation of DNAJB1-PRKACA fusion neoantigens by different HLA class I alleles


ABSTRACT: Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in this disease is its highly conserved driver mutation: a gene fusion between DNAJB1 and PRKACA, which is expressed in virtually all FLC tumors and could be an ideal neoantigen target for immunotherapy. In this study, we aimed to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) as candidates for novel cellular immunotherapies. Although fusion-specific T cells in FLC appear to be rare, we nevertheless defined an endogenous functional T cell response in an FLC patient.

INSTRUMENT(S): timsTOF Pro 2

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte, Cell Culture

DISEASE(S): Fibrolamellar Carcinoma

SUBMITTER: Kirti Pandey  

LAB HEAD: Anthony Wayne Purcell

PROVIDER: PXD042316 | Pride | 2024-05-24

REPOSITORIES: Pride

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Publications

DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.

Kirk Allison M AM   Crawford Jeremy Chase JC   Chou Ching-Heng CH   Guy Cliff C   Pandey Kirti K   Kozlik Tanya T   Shah Ravi K RK   Chung Shanzou S   Nguyen Phuong P   Zhang Xiaoyu X   Wang Jin J   Bell Matthew M   Mettelman Robert C RC   Allen E Kaitlynn EK   Pogorelyy Mikhail V MV   Kim Hyunjin H   Minervina Anastasia A AA   Awad Walid W   Bajracharya Resha R   White Toni T   Long Donald D   Gordon Brittney B   Morrison Michelle M   Glazer Evan S ES   Murphy Andrew J AJ   Jiang Yixing Y   Fitzpatrick Elizabeth A EA   Yarchoan Mark M   Sethupathy Praveen P   Croft Nathan P NP   Purcell Anthony W AW   Federico Sara M SM   Stewart Elizabeth E   Gottschalk Stephen S   Zamora Anthony E AE   DeRenzo Christopher C   Strome Scott E SE   Thomas Paul G PG  

Cell reports. Medicine 20240301 3


Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies. We observe that fusion-specific CD8 T cells a  ...[more]

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