{"doi":"10.1038/s41586-018-0792-9","title":"Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial","abstract":"Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses<sup>1,2</sup> and can function as bona fide antigens that facilitate tumour rejection<sup>3</sup>. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma<sup>4-6</sup>, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load<sup>1,7</sup> and an immunologically 'cold' tumour microenvironment<sup>8</sup>. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone-a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma-generated circulating polyfunctional neoantigen-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma.","journal":"Nature","year":2018,"id":11110,"datarank":1.0880205574026793,"base_score":7.253470382684528,"endowment":7.253470382684528,"self_citation_contribution":1.0880205574026793,"citation_network_contribution":0.0,"self_endowment_contribution":1.0880205574026793,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1412,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.053,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2018-12-19","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":25285,"name":"Jing Sun","orcid":"0000-0002-4320-1377","position":2,"is_corresponding":false},{"id":2735,"name":"Itay Tirosh","orcid":"0000-0001-5477-2987","position":3,"is_corresponding":false},{"id":25162,"name":"Nathan D. 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