4.6 Article

CSPG4 Expression in GIST Is Associated with Better Prognosis and Strong Cytotoxic Immune Response

期刊

CANCERS
卷 14, 期 5, 页码 -

出版社

MDPI
DOI: 10.3390/cancers14051306

关键词

CSPG4; gene expression; GIST; immune response; prognosis; CAR-CIKs; NK cells

类别

向作者/读者索取更多资源

Gastrointestinal stromal tumors (GIST) are the most frequent sarcomas of the gastrointestinal tract. This study found that high expression of cell surface proteoglycan CSPG4 in GIST is associated with better disease-free survival and an immune environment favorable to cytotoxic immune response. These findings suggest the potential value of CSPG4-specific chimeric antigen receptor-redirected cytokine-induced killer lymphocytes treatment in GIST, especially in CSPG4-high tumors, and calls for further validation and clinical trials.
Simple Summary Gastrointestinal stromal tumors (GIST) are the most frequent sarcomas of the gastrointestinal tract. Identification of novel prognostic and/or therapeutic targets is a major issue to overcome tyrosine kinase inhibitors resistances. CSPG4, a cell surface proteoglycan, emerged as a potential therapeutic target for immune therapy in different cancers, including sarcomas. CSPG4 expression has never been studied in GIST. In this work we analyzed CSPG4 mRNA expression in a large series of clinical GIST samples given the scarcity of disease (n = 309 patients). We find that high CSPG4 expression is independently associated with disease-free survival, and with an immune landscape favorable to induce strong cytotoxic immune response after NK cell stimulation. Our results suggest the potential value of CSPG4-specific chimeric antigen receptor-redirected cytokine-induced killer lymphocytes treatment in GIST, notably CSPG4-high tumors, and calls for preclinical validation, drug testing in vivo, then in clinical trials. The treatment of gastrointestinal stromal tumors (GIST) must be improved through the development of more reliable prognostic factors and of therapies able to overcome imatinib resistance. The immune system represents an attractive tool. CSPG4, a cell surface proteoglycan, emerged as a potential therapeutic target for immune therapy in different cancers, including cell therapy based on CSPG4-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CSPG4-CAR.CIKs) in sarcomas. CSPG4 expression has never been studied in GIST. We analyzed CSPG4 mRNA expression data of 309 clinical GIST samples profiled using DNA microarrays and searched for correlations with clinicopathological and immune features. CSPG4 expression, higher in tumors than normal digestive tissues, was heterogeneous across tumors. High expression was associated with AFIP low-risk, gastric site, and localized stage, and independently with longer postoperative disease-free survival (DFS) in localized stage. The correlations between CSPG4 expression and immune signatures highlighted a higher anti-tumor immune response in CSPG4-high tumors, relying on both the adaptive and innate immune system, in which the boost of NK cells by CSPG4-CAR.CIKs might be instrumental, eventually combined with immune checkpoint inhibitors. In conclusion, high CSPG4 expression in GIST is associated with better DFS and offers an immune environment favorable to a vulnerability to CAR.CIKs.

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