4.6 Article

HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer

期刊

CANCERS
卷 14, 期 14, 页码 -

出版社

MDPI
DOI: 10.3390/cancers14143495

关键词

HSPG2 mutations; immunotherapy; melanoma; NSCLC; clinical biomarker; cancer genomics

类别

资金

  1. Medicine and Health Science and Technology Development Plan Project of Shandong Province [202112050480]
  2. National Natural Science Foundation of China [32000495]
  3. Natural Science Foundation of Shandong Province [ZR2020MH202]

向作者/读者索取更多资源

Immune checkpoint inhibitors significantly improve the survival outcomes of advanced melanoma and non-small cell lung cancer. This study identifies HSPG2 mutations as potential clinical biomarkers for evaluating the efficacy of immune checkpoint inhibitor therapy. HSPG2 mutations are associated with favorable tumor immunogenicity and immunotherapeutic efficacy.
Simple Summary Immune checkpoint inhibitors (ICIs) markedly improve the survival benefits of advanced melanoma and non-small cell lung cancer (NSCLC). Nevertheless, only a subset of patients could benefit from such a therapy. Novel and effective clinical biomarkers are needed to assess ICI treatment efficacy. Heparan sulfate proteoglycan 2 (HSPG2) is frequently mutated in melanoma and NSCLC. In this study, we comprehensively integrated the pretreatment somatic mutational profiles and clinical information of both tumors and observed that HSPG2 mutations were associated with favorable tumor immunogenicity and immunotherapeutic efficacy. Our study provides a potential clinical molecular biomarker for evaluating ICI therapy responses. Immune checkpoint inhibitors (ICIs) markedly promote the survival outcome of advanced melanoma and non-small cell lung cancer (NSCLC). Clinically, favorable ICI treatment efficacy is noticed only in a smaller proportion of patients. Heparan sulfate proteoglycan 2 (HSPG2) frequently mutates in both tumors. Herein, we aim to investigate the immunotherapeutic and immunological roles of HSPG2 mutations in melanoma and NSCLC. A total of 631 melanoma samples and 109 NSCLC samples with both somatic mutational profiles and clinical immunotherapy data were curated. In addition, by using The Cancer Genome Atlas data, genomic and immunological traits behind HSPG2 mutations were elucidated. Melanoma patients with HSPG2 mutations had a markedly extended ICI outcome than other patients. An association between HSPG2 mutations and the improved outcome was further confirmed in NSCLC. In addition, an elevated ICI response rate was presented in HSPG2-mutated NSCLC patients (81.8% vs. 29.7%, p = 0.002). Subsequent analyses revealed that HSPG2-mutated patients had a favorable abundance of response immunocytes, an inferior abundance of suppression immunocytes, enhanced mutational burden, and interferon response-relevant signaling pathways. We uncovered that HSPG2 mutations were predictive of a better ICI response and associated with preferable immunogenicity, which may be considered as a genomic determinant to customize biotherapy strategies.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据