Stromal localization of inactive CD8 + T cells in metastatic mismatch repair deficient colorectal cancer.

Autor:	Küçükköse E; Division of Imaging and Cancer, Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Baars MJD; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Amini M; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.; UCyTOF.nl, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Schraa SJ; Division of Imaging and Cancer, Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Floor E; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Bol GM; Division of Imaging and Cancer, Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Borel Rinkes IHM; Division of Imaging and Cancer, Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Roodhart JML; Division of Imaging and Cancer, Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.; Division of Imaging and Cancer, Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Koopman M; Division of Imaging and Cancer, Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Laoukili J; Division of Imaging and Cancer, Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Kranenburg O; Division of Imaging and Cancer, Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, The Netherlands. o.kranenburg@umcutrecht.nl.; Utrecht Platform for Organoid Technology, Utrecht University, Utrecht, The Netherlands. o.kranenburg@umcutrecht.nl., Vercoulen Y; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. y.vercoulen@umcutrecht.nl.; UCyTOF.nl, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. y.vercoulen@umcutrecht.nl.
Jazyk:	angličtina
Zdroj:	British journal of cancer [Br J Cancer] 2024 Feb; Vol. 130 (2), pp. 213-223. Date of Electronic Publication: 2023 Dec 02.
DOI:	10.1038/s41416-023-02500-x
Abstrakt:	Background: The determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in primary tumors may discriminate between non-metastatic MSI-H CRC and metastatic MSI-H CRC. Methods: We profiled 46,727 single cells using high-plex imaging mass cytometry and analyzed both differential cell type abundance, and spatial distribution of fibroblasts and immune cells in primary CRC tumors with or without metastatic capacity. We validated our findings in a second independent cohort using immunohistochemistry. Results: High-plex imaging mass cytometry and hierarchical clustering based on microenvironmental markers separated primary MSI-H CRC tumors with and without metastatic capacity. Primary tumors with metastatic capacity displayed a high stromal content and low influx of CD8 + T cells, which expressed significantly lower levels of markers reflecting proliferation (Ki67) and antigen-experience (CD45RO) compared to CD8 + T cells in non-metastatic tumors. CD8 + T cells showed intra-epithelial localization in non-metastatic tumors, but stromal localization in metastatic tumors, which was validated in a second cohort. Conclusion: We conclude that localization of phenotypically distinct CD8 + T cells within stroma may predict metastasis formation in MSI-H CRC. (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink