This website requires JavaScript.
DOI: 10.1101/2023.05.20.23290277

The interplay between neoantigens and immune cells in sarcomas treated with checkpoint inhibition

I.Anzar B. Malone P. Samarakoon ...+9 T. Clancy
摘要
Sarcomas are comprised of diverse bone and connective tissue tumors with few effective therapeutic options for locally advanced unresectable and/or metastatic disease. Recent advances in immunotherapy, in particular immune checkpoint inhibition (ICI), have shown promising outcomes in several cancer indications. Unfortunately, ICI therapy has provided only modest clinical responses and seems moderately effective in a subset of the diverse subtypes. To explore the immune parameters governing ICI therapy resistance or immune escape, we performed whole exome sequencing (WES) on tumors and their matched normal blood, in addition to RNA-seq from tumors of 31 sarcoma patients treated with pembrolizumab. We used advanced computational methods to investigate key immune properties, such as neoantigens and immune cell composition in the tumor microenvironment (TME). A multifactorial analysis suggested that expression of high quality neoantigens in the context of specific immune cells in the TME are key prognostic markers of progression-free survival (PFS). The presence of several types of immune cells, including T cells, B cells and macrophages, in the TME were associated with improved PFS. Importantly, we also found the presence of both CD8+ T cells and neoantigens together was associated with improved survival compared to the presence of CD8+ T cells or neoantigens alone. Interestingly, this trend was not identified with the combined presence of CD8+ T cells and TMB; suggesting that a combined CD8+ T cell and neoantigen effect on PFS was important. The outcome of this study may inform future trials that may lead to improved outcomes for sarcoma patients treated with ICI.
展开全部
图表提取

暂无人提供速读十问回答

论文十问由沈向洋博士提出，鼓励大家带着这十个问题去阅读论文，用有用的信息构建认知模型。写出自己的十问回答，还有机会在当前页面展示哦。

Q1论文试图解决什么问题？
Q2这是否是一个新的问题？
Q3这篇文章要验证一个什么科学假设？
0
被引用
0
笔记
0
问答