Dynamic Profiling of the Immune Tumor Microenvironment in Locally Advanced Gastric Cancer Treated with Perioperative Chemotherapy.

Autor:	Pecora I; Unit of Medical Oncology, Ospedale Misericordia, Azienda USL Toscana Sud Est, Grosseto, Italy., Ugolini C; Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy., Giannini R; Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy., Giordano M; Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy., Vivaldi C; Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy., Lencioni M; Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Santi S; Unit of Esophageal Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Massa V; Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Pallabazzer G; Unit of Esophageal Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Catanese S; Unit of Medical Oncology, Ospedale Misericordia, Azienda USL Toscana Sud Est, Grosseto, Italy., Salani F; Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.; Sant'Anna School of Advanced Studies, Pisa, Italy., Belluomini MA; Unit of Esophageal Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Vasile E; Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Cremolini C; Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy., Fontanini G; Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy., Masi G; Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Fornaro L; Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Jazyk:	angličtina
Zdroj:	Oncology [Oncology] 2023; Vol. 101 (7), pp. 435-445. Date of Electronic Publication: 2023 Jun 12.
DOI:	10.1159/000530853
Abstrakt:	Introduction: 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. Methods: 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. Results: 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. Conclusion: 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. (© 2023 S. Karger AG, Basel.)
Databáze:	MEDLINE
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