Mutational and neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma
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ABSTRACT: Purpose: Utility of immunological treatment in cancer has increased; however, many patients do not respond to treatment. Identification of robust predictive biomarkers is required to correctly stratify patients. Although clinical trials based on adoptive T cell therapy (ACT) have yielded high response rates and many durable responses in melanoma, 50-60% of the patients have no clinical benefit. Herein, we searched for predictive biomarkers to ACT in melanoma. Methods: Whole exome- and transcriptome sequencing, neoantigen prediction and immune cell signature analysis were applied to pre-treatment melanoma samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously been treated with other immunotherapies. Results: We found that clinical benefit was associated with significantly higher neoantigen load (P=0.025). High mutation and neoantigen load were significantly associated with improved progression-free and overall survival (P=8x10^-4 and P=0.001, respectively). Further, gene-expression analysis of pre-treatment biopsies showed that clinical benefit was associated with strong immune activation signatures including a high MHC-I antigen processing and presentation score. Conclusions: These results improve our understanding of clinical benefit of ACT in melanoma, which can lead to clinically useful predictive biomarkers to be used for selecting patients that benefit from these highly intensive treatment regimens.
ORGANISM(S): Homo sapiens
PROVIDER: GSE100797 | GEO | 2017/12/04
SECONDARY ACCESSION(S): PRJNA393105
REPOSITORIES: GEO
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