免疫系统
肿瘤微环境
免疫疗法
医学
CD8型
化疗
原发性肿瘤
肿瘤科
癌症研究
癌症
内科学
免疫学
转移
作者
Irene Pecora,Clara Ugolini,Raffaello Giannini,Mirella Giordano,Caterina Vivaldi,M. Lencioni,Stefano Santi,Valentina Massa,Giovanni Pallabazzer,Silvia Catanese,Francesca Salani,Mario Antonio Belluomini,Enrico Vasile,Chiara Cremolini,Gabriella Fontanini,Gianluca Masi,Lorenzo Fornaro
出处
期刊:Oncology
[S. Karger AG]
日期:2023-01-01
卷期号:101 (7): 435-445
摘要
In locally advanced gastric cancer (GC), FLOT represents the standard perioperative regimen and combination with immunotherapy is under investigation. However, the role of immune tumor microenvironment (TME) is poorly recognized in this setting. We aimed to study TME characteristics and dynamics during FLOT.Paired biopsy (PRE) and surgical (POST) samples of 25 patients treated with FLOT were prospectively analyzed. After collection of clinic-pathological data, NanoString analyses were performed. The primary objective of the study was to assess the changes induced by chemotherapy in POST compared to PRE samples.The unsupervised hierarchical method analysis clearly distinguished PRE and POST samples, even though some cases showed high immune gene expression at baseline. When POST samples were compared with PRE, a differential expression in hyper-expressed gene sets related to cytotoxicity, T-cell functions, complement system, tumor necrosis factor superfamily, cell cycle, and regulation was recognized. Downstaging of the primary tumor (T-regression, measured by pathologic compared to clinical T stage) was the covariate most frequently associated with these changes. Using the immune cell profiling, cases with T-regression reported a significant increase of T, CD8+ T and B cells and a decrease in mast cells, while nonresponders demonstrated an increase of T, B, cytotoxic, and mast cells.Our analysis shows that FLOT significantly influences immune TME of GC. While relevant modifications preferentially occur in tumors showing primary tumor regression, response to treatment seems to be associated with a specific immune profile.
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