Current treatment for patients with locally advanced esophageal adenocarcinoma (EAC) is neoadjuvant chemotherapy (nCT), alone or combined with radiotherapy, before surgery. However, fewer than 30% of treated patients show a pathological complete response to nCT, which correlates with increased 5-year survival compared to non-responders. Understanding the mechanisms of response to nCT is pivotal to better stratify patients and inform more efficacious therapies. Here, we investigated the immune mechanisms involved in nCT response by multi-dimensional profiling of pre-treatment tumor biopsies and blood from 68 EAC patients (34 prospectively and 34 retrospectively collected), comparing complete responders versus non-responders to nCT. At the tumor level, complete response to nCT was associated with molecular signatures of immune response and proliferation, increased putative anti-tumor tissue-resident memory CD39+CD103+CD8+ T cells and reduced immunosuppressive T regulatory cells and M2-like macrophages. Systemically, complete responders showed higher frequencies of immunostimulatory CD14+CD11c+HLA-DRhigh cells and reduced PDL1+ monocytic myeloid-derived suppressor cells, along with high plasma GM-CSF (pro-inflammatory) and low IL-4, CXCL10, C3a, and C5a (suppressive). Plasma pro-inflammatory and suppressive cytokines correlated directly and inversely, respectively, with the frequency of tumor-infiltrating CD39+CD103+CD8+ T cells. These results suggest that pre-existing immunity in baseline tumors drives the clinical activity of nCT in locally advanced EAC. Furthermore, it may be possible to stratify patients based on predictive immune signatures, enabling tailored neoadjuvant and/or adjuvant regimens.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。