Dataset Information

Identification and ranking of recurrent neo-epitopes in cancer.

ABSTRACT: BACKGROUND:Immune escape is one of the hallmarks of cancer and several new treatment approaches attempt to modulate and restore the immune system's capability to target cancer cells. At the heart of the immune recognition process lies antigen presentation from somatic mutations. These neo-epitopes are emerging as attractive targets for cancer immunotherapy and new strategies for rapid identification of relevant candidates have become a priority. METHODS:We carefully screen TCGA data sets for recurrent somatic amino acid exchanges and apply MHC class I binding predictions. RESULTS:We propose a method for in silico selection and prioritization of candidates which have a high potential for neo-antigen generation and are likely to appear in multiple patients. While the percentage of patients carrying a specific neo-epitope and HLA-type combination is relatively small, the sheer number of new patients leads to surprisingly high reoccurence numbers. We identify 769 epitopes which are expected to occur in 77629 patients per year. CONCLUSION:While our candidate list will definitely contain false positives, the results provide an objective order for wet-lab testing of reusable neo-epitopes. Thus recurrent neo-epitopes may be suitable to supplement existing personalized T cell treatment approaches with precision treatment options.

SUBMITTER: Blanc E

PROVIDER: S-EPMC6882202 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Identification and ranking of recurrent neo-epitopes in cancer.

Blanc Eric E Holtgrewe Manuel M Dhamodaran Arunraj A Messerschmidt Clemens C Willimsky Gerald G Blankenstein Thomas T Beule Dieter D

BMC medical genomics 20191127 1

<h4>Background</h4>Immune escape is one of the hallmarks of cancer and several new treatment approaches attempt to modulate and restore the immune system's capability to target cancer cells. At the heart of the immune recognition process lies antigen presentation from somatic mutations. These neo-epitopes are emerging as attractive targets for cancer immunotherapy and new strategies for rapid identification of relevant candidates have become a priority.<h4>Methods</h4>We carefully screen TCGA da ...[more]

PMID: 31775766

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Project description:ObjectivesTo evaluate incidence, predictors, and re-treatment outcome of recurrent myopic choroidal neovascularization (m-CNV).MethodsRetrospective consecutive observational series. From year 2014 to 2019, 167 eyes of 167 patients of treatment naïve m-CNV were enrolled. 59 and 108 eyes were treated with intra-vitreal ranibizumab and bevacizumab mono-therapy, respectively. Recurrence was defined as re-appearance of CNV activity, confirmed on optical coherence tomography (OCT) after at least 3 months of cessation of anti-VEGF therapy. Incidence of recurrence, predictors and re-treatment outcomes were studied.ResultsOverall, mean age and spherical equivalence (SE) was 47.95 ± 14.72 years and -12.19 ± 4.93 D respectively. Males constituted 50.9%. 44 eyes (26.4%) had a recurrence during a mean follow up of 16.5 ± 12.86 months. Kaplan-Meier survival analysis showed the risk of recurrence was 8, 26 and, 33.6% at 6, 12 and 18 months, respectively. Age (p = 0.511), gender (p = 0.218), SE (p = 0.092), anti-VEGF (p = 0.629) and baseline BCVA (p = 0.519) did not influence recurrence. Number of injections administered to control the disease in the first episode was the only significant predictor of recurrence (Cox Proportional Hazard Ratio 2.89-3.07, 95% Confidence Interval: 1.28-7.45; p = 0.005). At 12 months, eyes requiring one injection in first episode had a recurrence rate of 12% versus 45% in eyes requiring 3 or more injections in the first episode. A mean number of 1.9 additional injections per eye was needed during re-treatment. Final BCVA in the recurrence group was similar to that of non-recurrence group (0.53 ± 0.40 versus 0.55 ± 0.36 LogMAR; p = 0.755). Baseline BCVA (p = 0.0001) was the only predictor of final visual outcome irrespective of anti-VEGF drug (p = 0.38).ConclusionEyes requiring greater number of injections for disease control in first episode are "at risk" of early m-CNV recurrence. However, recurrence does not adversely affect visual outcome, if treated adequately.

Dataset Information

Identification and ranking of recurrent neo-epitopes in cancer.

Publications

Identification and ranking of recurrent neo-epitopes in cancer.

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