Alpha 2.0
Login Register
» Articles » PMID: 38611111

Identifying the Spatial Architecture That Restricts the Proximity of CD8 T Cells to Tumor Cells in Pancreatic Ductal Adenocarcinoma

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2024 Apr 13
PMID 38611111
Authors
Yihan Xia
Junrui Ma
Xiaobao Yang
Danping Liu
Yujie Zhu
Yanan Zhao
Xuefeng Fei
Dakang Xu
Jing Dai
Affiliations
Soon will be listed here.
Abstract

The anti-tumor function of CD8 T cells is dependent on their proximity to tumor cells. Current studies have focused on the infiltration level of CD8 T cells in the tumor microenvironment, while further spatial information, such as spatial localization and inter-cellular communication, have not been defined. In this study, co-detection by indexing (CODEX) was designed to characterize PDAC tissue regions with seven protein markers in order to identify the spatial architecture that regulates CD8 T cells in human pancreatic ductal adenocarcinoma (PDAC). The cellular neighborhood algorithm was used to identify a total of six conserved and distinct cellular neighborhoods. Among these, one unique spatial architecture of CD8 T and CD4 T cell-enriched neighborhoods enriched the majority of CD8 T cells, but heralded a poor prognosis. The proximity analysis revealed that the CD8 T cells in this spatial architecture were significantly closer to themselves and the CD4 T cells than to the tumor cells. Collectively, we identified a unique spatial architecture that restricted the proximity of CD8 T cells to tumor cells in the tumor microenvironment, indicating a novel immune evasion mechanism of pancreatic ductal adenocarcinoma in a topologically regulated manner and providing new insights into the biology of PDAC.

References
1.
Nevala-Plagemann C, Hidalgo M, Garrido-Laguna I . From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer. Nat Rev Clin Oncol. 2019; 17(2):108-123. DOI: 10.1038/s41571-019-0281-6. View
2.
Goltsev Y, Nolan G . CODEX multiplexed tissue imaging. Nat Rev Immunol. 2023; 23(10):613. DOI: 10.1038/s41577-023-00936-z. View
3.
Bandura D, Baranov V, Ornatsky O, Antonov A, Kinach R, Lou X . Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal Chem. 2009; 81(16):6813-22. DOI: 10.1021/ac901049w. View
4.
Link A, Hardie D, Favre S, Britschgi M, Adams D, Sixt M . Association of T-zone reticular networks and conduits with ectopic lymphoid tissues in mice and humans. Am J Pathol. 2011; 178(4):1662-75. PMC: 3070229. DOI: 10.1016/j.ajpath.2010.12.039. View
5.
Binnewies M, Roberts E, Kersten K, Chan V, Fearon D, Merad M . Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018; 24(5):541-550. PMC: 5998822. DOI: 10.1038/s41591-018-0014-x. View