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新辅助/围手术期治疗影响胃癌中肿瘤相关中性粒细胞和CD8+淋巴细胞的空间分布及密度。

Neoadjuvant/Perioperative Treatment Affects Spatial Distribution and Densities of Tumor Associated Neutrophils and CD8+ Lymphocytes in Gastric Cancer.

作者信息

Hoffmann Anne, Behrens Hans-Michael, Heckl Steffen, Krüger Sandra, Becker Thomas, Röcken Christoph

机构信息

Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel, Germany.

Department of Internal Medicine II, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel, Germany.

出版信息

J Pers Med. 2021 Nov 12;11(11):1184. doi: 10.3390/jpm11111184.

DOI:10.3390/jpm11111184
PMID:34834537
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8622782/
Abstract

Tumor associated neutrophils (TANs) and cytotoxic T cells (CTLs) are part of the tumor microenvironment of gastric cancer (GC). We explored their tumor biological significance in neoadjuvantly/perioperatively treated GC. Immunostaining was performed on whole tissue sections of 173 GCs, using antibodies directed against myeloperoxidase (MPO) and CD8. Stained specimens were digitalized, and the densities of TANs and CTLs were assessed separately in the mucosa, tumor surface, tumor center, invasion front, and tumor scar. The densities were correlated with clinicopathological patient characteristics. Compared with a historical cohort of 449 treatment naive GCs, the TAN density in the invasion front was significantly lower in neoadjuvantly/perioperatively treated GCs. TAN density in the tumor center and invasion front correlated with tumor regression. TAN density also correlated with CTL density in the tumor center and invasion front. A high density of CTL in the tumor center correlated with an improved overall survival and tumor specific survival. We show that neoadjuvant/perioperative (radio-) chemotherapy impacts on the immune microenvironment of GC, while also depending on sex. The density of TANs in neoadjuvantly/perioperatively treated GCs differed from findings made in a treatment naive GC cohort.

摘要

肿瘤相关中性粒细胞(TANs)和细胞毒性T细胞(CTLs)是胃癌(GC)肿瘤微环境的一部分。我们探讨了它们在新辅助/围手术期治疗的GC中的肿瘤生物学意义。使用针对髓过氧化物酶(MPO)和CD8的抗体,对173例GC的全组织切片进行免疫染色。对染色标本进行数字化处理,并分别评估黏膜、肿瘤表面、肿瘤中心、浸润前沿和肿瘤瘢痕中TANs和CTLs的密度。这些密度与患者的临床病理特征相关。与449例未经治疗的GC历史队列相比,新辅助/围手术期治疗的GC浸润前沿的TAN密度显著降低。肿瘤中心和浸润前沿的TAN密度与肿瘤退缩相关。肿瘤中心和浸润前沿的TAN密度也与CTL密度相关。肿瘤中心高CTL密度与总体生存率和肿瘤特异性生存率的提高相关。我们表明,新辅助/围手术期(放)化疗会影响GC的免疫微环境,同时也取决于性别。新辅助/围手术期治疗的GC中TANs的密度与未经治疗的GC队列中的结果不同。

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N Engl J Med. 2021 Apr 1;384(13):1191-1203. doi: 10.1056/NEJMoa2032125.
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