B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes

The immunotherapies based on ICIs in CRC are nowadays limited to microsatellite unstable tumours which are approximately 15% of all CRC cases. There are a few new immune checkpoints belonging to the B7 family, including B7H4. B7H4 expression is associated with so-called “cold tumours”, and its funct...

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Main Authors: Miriam Dawidowicz, Agnieszka Kula, Sylwia Mielcarska, Paweł Kiczmer, Hanna Skiba, Małgorzata Krygier, Magdalena Chrabańska, Jerzy Piecuch, Monika Szrot, Julia Robotycka, Błażej Ochman, Bogumiła Strzałkowska, Zenon Czuba, Elżbieta Świętochowska, Dariusz Waniczek
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/6/861
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author Miriam Dawidowicz
Agnieszka Kula
Sylwia Mielcarska
Paweł Kiczmer
Hanna Skiba
Małgorzata Krygier
Magdalena Chrabańska
Jerzy Piecuch
Monika Szrot
Julia Robotycka
Błażej Ochman
Bogumiła Strzałkowska
Zenon Czuba
Elżbieta Świętochowska
Dariusz Waniczek
author_facet Miriam Dawidowicz
Agnieszka Kula
Sylwia Mielcarska
Paweł Kiczmer
Hanna Skiba
Małgorzata Krygier
Magdalena Chrabańska
Jerzy Piecuch
Monika Szrot
Julia Robotycka
Błażej Ochman
Bogumiła Strzałkowska
Zenon Czuba
Elżbieta Świętochowska
Dariusz Waniczek
author_sort Miriam Dawidowicz
collection DOAJ
description The immunotherapies based on ICIs in CRC are nowadays limited to microsatellite unstable tumours which are approximately 15% of all CRC cases. There are a few new immune checkpoints belonging to the B7 family, including B7H4. B7H4 expression is associated with so-called “cold tumours”, and its function is linked to the downregulation of various immune cell populations. Our study aimed to investigate whether B7H4 expression is dependent on microsatellite status in CRC and on elucidating the immunological context in which the expression of B7H4 occurs. We enrolled 167 patients in the study. We prepared the homogenates from tumour tissues and healthy adjacent tissue to assess the B7H4 levels and the Bio-Plex Pro Human 48-cytokine panel. We assessed the microsatellite status of the tumour, B7H4 expression, CD8+ T cell population, and the TILs and budding in H + E stained slides by the IHC method. We used an online available database for further exploring the biological characteristics of B7H4. The expression of B7H4 was more frequent in microsatellite stable tumours, and was negatively associated with TILs. B7H4 is positively correlated with antitumour immunosuppressive iTME, thus contributing to the immunosuppressive environment in CRC.
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spelling doaj.art-147726ee48eb410f85c371a76bc169972023-11-17T10:12:53ZengMDPI AGCells2073-44092023-03-0112686110.3390/cells12060861B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating LymphocytesMiriam Dawidowicz0Agnieszka Kula1Sylwia Mielcarska2Paweł Kiczmer3Hanna Skiba4Małgorzata Krygier5Magdalena Chrabańska6Jerzy Piecuch7Monika Szrot8Julia Robotycka9Błażej Ochman10Bogumiła Strzałkowska11Zenon Czuba12Elżbieta Świętochowska13Dariusz Waniczek14Department of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Ksatowice, PolandDepartment of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Ksatowice, PolandDepartment of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 19 Jordana, 41-800 Zabrze, PolandDepartment and Chair of Pathomorphology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 13-15 3 Maja, 41-800 Zabrze, PolandDepartment and Chair of Pathomorphology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 13-15 3 Maja, 41-800 Zabrze, PolandDepartment and Chair of Pathomorphology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 13-15 3 Maja, 41-800 Zabrze, PolandDepartment and Chair of Pathomorphology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 13-15 3 Maja, 41-800 Zabrze, PolandDepartment of General and Bariatric Surgery and Emergency Medicine, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Katowice, PolandDepartment of General and Bariatric Surgery and Emergency Medicine, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Katowice, PolandDepartment of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 19 Jordana, 41-800 Zabrze, PolandDepartment of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 19 Jordana, 41-800 Zabrze, PolandDepartment of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 19 Jordana, 41-800 Zabrze, PolandDepartment of Microbiology and Immunology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, PolandDepartment of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 19 Jordana, 41-800 Zabrze, PolandDepartment of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Ksatowice, PolandThe immunotherapies based on ICIs in CRC are nowadays limited to microsatellite unstable tumours which are approximately 15% of all CRC cases. There are a few new immune checkpoints belonging to the B7 family, including B7H4. B7H4 expression is associated with so-called “cold tumours”, and its function is linked to the downregulation of various immune cell populations. Our study aimed to investigate whether B7H4 expression is dependent on microsatellite status in CRC and on elucidating the immunological context in which the expression of B7H4 occurs. We enrolled 167 patients in the study. We prepared the homogenates from tumour tissues and healthy adjacent tissue to assess the B7H4 levels and the Bio-Plex Pro Human 48-cytokine panel. We assessed the microsatellite status of the tumour, B7H4 expression, CD8+ T cell population, and the TILs and budding in H + E stained slides by the IHC method. We used an online available database for further exploring the biological characteristics of B7H4. The expression of B7H4 was more frequent in microsatellite stable tumours, and was negatively associated with TILs. B7H4 is positively correlated with antitumour immunosuppressive iTME, thus contributing to the immunosuppressive environment in CRC.https://www.mdpi.com/2073-4409/12/6/861B7H4microsatellite stable tumoursiTMECRCimmune checkpoint
spellingShingle Miriam Dawidowicz
Agnieszka Kula
Sylwia Mielcarska
Paweł Kiczmer
Hanna Skiba
Małgorzata Krygier
Magdalena Chrabańska
Jerzy Piecuch
Monika Szrot
Julia Robotycka
Błażej Ochman
Bogumiła Strzałkowska
Zenon Czuba
Elżbieta Świętochowska
Dariusz Waniczek
B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes
Cells
B7H4
microsatellite stable tumours
iTME
CRC
immune checkpoint
title B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes
title_full B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes
title_fullStr B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes
title_full_unstemmed B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes
title_short B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes
title_sort b7h4 expression is more frequent in mss status colorectal cancer and is negatively associated with tumour infiltrating lymphocytes
topic B7H4
microsatellite stable tumours
iTME
CRC
immune checkpoint
url https://www.mdpi.com/2073-4409/12/6/861
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