Dataset Information

Neoantigen landscape in metastatic nasopharyngeal carcinoma.

ABSTRACT: Background: Reportedly, nasopharyngeal carcinoma (NPC) patients with MHC I Class aberration are prone to poor survival outcomes, which indicates that the deficiency of tumor neoantigens might represent a mechanism of immune surveillance escape in NPC. Methods: To clearly delineate the landscape of neoantigens in NPC, we performed DNA and RNA sequencing on paired primary tumor, regional lymph node metastasis and distant metastasis samples from 26 patients. Neoantigens were predicted using pVACseq pipeline. Subtype prediction model was built using random forest algorithm. Results: Portraying the landscape of neoantigens in NPC for the first time, we found that the neoantigen load of NPC was above average compared to that of other cancers in The Cancer Genome Atlas program. While the quantity and quality of neoantigens were similar among primary tumor, regional lymph node metastasis and distant metastasis samples, neoantigen depletion was more severe in metastatic sites than in primary tumors. Upon tracking the clonality change of neoantigens, we found that neoantigen reduction occurred during metastasis. Building a subtype prediction model based on reported data, we observed that subtype I lacked T cells and suffered from severe neoantigen depletion, subtype II highly expressed immune checkpoint molecules and suffered from the least neoantigen depletion, and subtype III was heterogenous. Conclusions: These results indicate that neoantigens are conducive to the guidance of clinical treatment, and personalized therapeutic vaccines for NPC deserve deeper basic and clinical investigations to make them feasible in the future.

SUBMITTER: Lin M

PROVIDER: S-EPMC8120206 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Neoantigen landscape in metastatic nasopharyngeal carcinoma.

Lin Mei M Zhang Xiao-Long XL You Rui R Yang Qi Q Zou Xiong X Yu Kai K Liu You-Ping YP Zou Ru-Hai RH Hua Yi-Jun YJ Huang Pei-Yu PY Wang Jin J Zhao Qi Q Jiang Xiao-Bing XB Tang Jun J Gu Yang-Kui YK Yu Tao T He Gui-Ping GP Xie Yu-Long YL Wang Zhi-Qiang ZQ Liu Ting T Chen Si-Yuan SY Zuo Zhi-Xiang ZX Chen Ming-Yuan MY

Theranostics 20210419 13

<b>Background:</b> Reportedly, nasopharyngeal carcinoma (NPC) patients with MHC I Class aberration are prone to poor survival outcomes, which indicates that the deficiency of tumor neoantigens might represent a mechanism of immune surveillance escape in NPC. <b>Methods:</b> To clearly delineate the landscape of neoantigens in NPC, we performed DNA and RNA sequencing on paired primary tumor, regional lymph node metastasis and distant metastasis samples from 26 patients. Neoantigens were predicted ...[more]

PMID: 33995666

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Project description:BackgroundThe majority of published studies in recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are single-arm trials. Reliable modelling of progression-free survival (PFS) and overall survival (OS) outcomes, therefore, is difficult. This study aim to analyse existent literature to estimate the relative efficacy of available systemic regimens in RM-NPC, as well as provide estimates of aggregate OS and PFS.MethodsWe conducted a systematic search of MEDLINE, EMBASE and the Cochrane Library to March 2015. Clinical trials (in English only) investigating cytotoxic and molecularly targeted agents in adult patients with RM-NPC were included. All relevant studies were assessed for quality using Downs and Blacks (DB) checklist (maximum quality score of 27). Aggregate data analysis and Student's t-test were performed for all identified studies (model A). For studies that published analysable Kaplan-Meier curves, survival data were extracted and marginal proportional hazards models were constructed (model B).ResultsA total of 56 studies were identified and included in model A, 26 of which had analysable Kaplan-Meier curves and were included in model B. The 26 studies in model B had significantly higher mean DB scores than the remaining 30 (17.3 vs 13.7, P=0.002). For patients receiving first line chemotherapy, the estimated median OS was 15.7 months by model A (95% CI, 12.3-19.1), and 19.3 months by model B (95% CI, 17.6-21.1). For patients undergoing second line or higher therapies (2nd+), the estimated median OS was 11.5 months by model A (95% CI 10.1-12.9), and 12.5 months by model B (95% CI 11.9-13.4). PFS estimates for patients undergoing first-line chemotherapy by model A was 7.6 months (95% CI, 6.2-9.0), and 8.0 months by model B (95% CI, 7.6-8.8). For patients undergoing therapy in the 2nd+ setting, the estimated PFS by model A was 5.4 months (95% CI, 3.8-7.0), and 5.2 months by model B (95% CI, 4.7-5.6).ConclusionsWe present the first aggregate estimates of OS and PFS for RM-NPC patients receiving first and second-line or higher treatment settings, which could inform the design of future clinical trials in this disease setting.

Project description:Hürthle cell carcinoma (HCC) is a rare type of thyroid cancer with high rates of distant metastasis and recurrence. Along with the scarcity of effective systemic therapies for HCC, these factors contribute to poor clinical outcomes. The immunologic features of HCC are poorly defined and response rates with immune checkpoint blockade have not been reported. A more comprehensive understanding of the immune landscape and factors that predict response to checkpoint inhibitors is needed. We performed RNA sequencing on 40 tumors to characterize the neoantigen landscape and immune microenvironment of HCC. We analyzed transcriptomic profiles, tumor-infiltrating immune cell populations, and measures of T-cell activation/dysfunction and correlated these to genetic features such as tumor mutation burden, neoantigen burden, mitochondrial mutations, and LOH from chromosomal uniparental disomy. Finally, immune profiles of patients with recurrence were compared with those of patients without recurrence. HCC tumors exhibited low levels of immune infiltration, with the more aggressive widely invasive phenotype associated with more immune depletion. There was a negative correlation between tumor mutation burden, neoantigen burden, programmed cell death ligand 1 (PD-L1) expression, and the immune infiltration score. HCC tumors that exhibited a global LOH from chromosomal uniparental disomy or haploidization had the lowest level of immune infiltration. HCC tumors that recurred displayed an immune-depleted microenvironment associated with global LOH and aerobic glycolysis. These findings offer new insights into the functional immune landscapes and immune microenvironment of HCC. Our data identify potential immunologic vulnerabilities for these understudied and often fatal cancers.SignificanceThe immune landscape of HCC is poorly defined and response rates to immunotherapy have not been reported. The authors found the immune microenvironment in HCC to be depleted. This immunosuppression is associated with a global LOH from haploidization and uniparental disomy, resulting in whole chromosome losses across the genome.

Dataset Information

Neoantigen landscape in metastatic nasopharyngeal carcinoma.

Publications

Neoantigen landscape in metastatic nasopharyngeal carcinoma.

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