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胰腺和其他壶腹周围腺癌中固有和半固有免疫细胞的拓扑分布和空间相互作用。

Topographical Distribution and Spatial Interactions of Innate and Semi-Innate Immune Cells in Pancreatic and Other Periampullary Adenocarcinoma.

机构信息

Department of Clinical Sciences Lund, Oncology and Therapeutic Pathology, Lund University, Lund, Sweden.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

出版信息

Front Immunol. 2020 Sep 10;11:558169. doi: 10.3389/fimmu.2020.558169. eCollection 2020.

DOI:10.3389/fimmu.2020.558169
PMID:33013928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7511775/
Abstract

BACKGROUND

The clinical management of pancreatic and other periampullary neoplasms remains challenging. In contrast to other cancer types, immunotherapies are largely ineffective, and the reason for the deprived immune response and the immune inhibiting cellular composition is only fragmentarily understood. The aim of this study was to comprehensively map the abundance, topographic distribution and spatial interaction of innate and innate-like immune cells in the tumor microenvironment of periampullary adenocarcinoma.

METHODS

Multiplexed immunofluorescent imaging was performed on tissue microarrays with tumors from a consecutive cohort of 175 patients with resected periampullary adenocarcinoma. To obtain a detailed spatial analysis of immune cell infiltration, two multiplex immune panels including antibodies against CD3, NKp46, CD56, CD68, CD163 and CD1a, CD208, CD123, CD15, CD68 and pan-cytokeratin were applied.

RESULTS

The infiltration of natural killer (NK) and NK-like T (NKT) cells was lower in malignant compared to benign tissue. NKT cells were more abundant in intestinal type compared to pancreatobiliary type tumors, and were associated with more favorable clinicopathological features and a prolonged survival. The interaction of NKp46 NKT cells with macrophages was also associated with a prolonged survival.

CONCLUSIONS

This study provides a comprehensive map of the innate immune landscape in periampullary adenocarcinoma. NK cells, and even more so NKT cells, are revealed to be central players in the local immune response in a clinically relevant context.

摘要

背景

胰腺和其他壶腹周围肿瘤的临床管理仍然具有挑战性。与其他癌症类型相比，免疫疗法的效果大多不佳，而免疫反应受到抑制和免疫细胞组成受到抑制的原因只是部分理解。本研究的目的是全面描绘壶腹周围腺癌肿瘤微环境中固有和固有样免疫细胞的丰度、拓扑分布和空间相互作用。

方法

对 175 例连续队列接受胰十二指肠切除术的壶腹周围腺癌患者的组织微阵列进行了多重免疫荧光成像。为了对免疫细胞浸润进行详细的空间分析，应用了包括针对 CD3、NKp46、CD56、CD68、CD163 和 CD1a、CD208、CD123、CD15、CD68 和泛细胞角蛋白的两种多重免疫组化试剂盒。

结果

与良性组织相比，恶性组织中自然杀伤（NK）和 NK 样 T（NKT）细胞的浸润较低。与胰胆管型肿瘤相比，NKT 细胞在肠型肿瘤中更为丰富，与更有利的临床病理特征和更长的生存时间相关。NKp46 NKT 细胞与巨噬细胞的相互作用也与延长生存时间相关。

结论

本研究提供了壶腹周围腺癌固有免疫图谱的全面描述。在临床相关背景下，NK 细胞，甚至 NKT 细胞，被揭示为局部免疫反应的核心参与者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/ae09b55a6f5e/fimmu-11-558169-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/c3bf4c223199/fimmu-11-558169-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/d38e700f98d9/fimmu-11-558169-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/2a66209f5471/fimmu-11-558169-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/c7bea30bf9aa/fimmu-11-558169-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/b131777de1c2/fimmu-11-558169-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/ae09b55a6f5e/fimmu-11-558169-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/c3bf4c223199/fimmu-11-558169-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/d38e700f98d9/fimmu-11-558169-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/2a66209f5471/fimmu-11-558169-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/c7bea30bf9aa/fimmu-11-558169-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/b131777de1c2/fimmu-11-558169-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a536/7511775/ae09b55a6f5e/fimmu-11-558169-g006.jpg

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