Antigen Presenting Cells from Tumor and Colon of Colorectal Cancer Patients Are Distinct in Activation and Functional Status, but Comparably Responsive to Activated T Cells
Although mouse models of CRC treatments have demonstrated robust immune activation, it remains unclear to what extent CRC patients’ APCs and TILs interact to fuel or quench treatment-induced immune responses. Our ex vivo characterization of tumor and adjacent colon cell suspensions suggest that cont...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/20/5247 |
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| author | Frank Liang Azar Rezapour Louis Szeponik Samuel Alsén Yvonne Wettergren Elinor Bexe Lindskog Marianne Quiding-Järbrink Ulf Yrlid |
| author_facet | Frank Liang Azar Rezapour Louis Szeponik Samuel Alsén Yvonne Wettergren Elinor Bexe Lindskog Marianne Quiding-Järbrink Ulf Yrlid |
| author_sort | Frank Liang |
| collection | DOAJ |
| description | Although mouse models of CRC treatments have demonstrated robust immune activation, it remains unclear to what extent CRC patients’ APCs and TILs interact to fuel or quench treatment-induced immune responses. Our ex vivo characterization of tumor and adjacent colon cell suspensions suggest that contrasting environments in these tissues promoted inversed expression of T cell co-stimulatory CD80, and co-inhibitory programmed death (PD)-ligand1 (PD-L1) on intratumoral vs. colonic APCs. While putative tumor-specific CD103+CD39+CD8+ TILs expressed lower CD69 (early activation marker) and higher PD-1 (extended activation/exhaustion marker) than colonic counterparts, the latter had instead higher CD69 and lower PD-1 levels. Functional comparisons showed that intratumoral APCs were inferior to colonic APCs regarding protein uptake and upregulation of CD80 and PD-L1 after protein degradation. Our attempt to model CRC treatment-induced T cell activation in vitro showed less interferon (IFN)-γ production by TILs than colonic T cells. In this model, we also measured APCs’ CD80 and PD-L1 expression in response to activated co-residing T cells. These markers were comparable in the two tissues, despite higher IFN- γ exposure for colonic APCs. Thus, APCs within distinct intratumoral and colonic milieus showed different activation and functional status, but were similarly responsive to signals from induced T cell activation. |
| first_indexed | 2024-03-10T06:40:42Z |
| format | Article |
| id | doaj.art-aa0f9f03bf914af6a9ec38ca1993506e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:40:42Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-aa0f9f03bf914af6a9ec38ca1993506e2023-11-22T17:42:42ZengMDPI AGCancers2072-66942021-10-011320524710.3390/cancers13205247Antigen Presenting Cells from Tumor and Colon of Colorectal Cancer Patients Are Distinct in Activation and Functional Status, but Comparably Responsive to Activated T CellsFrank Liang0Azar Rezapour1Louis Szeponik2Samuel Alsén3Yvonne Wettergren4Elinor Bexe Lindskog5Marianne Quiding-Järbrink6Ulf Yrlid7Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, SwedenDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska University Hospital, University of Gothenburg, 413 45 Gothenburg, SwedenDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska University Hospital, University of Gothenburg, 413 45 Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, SwedenAlthough mouse models of CRC treatments have demonstrated robust immune activation, it remains unclear to what extent CRC patients’ APCs and TILs interact to fuel or quench treatment-induced immune responses. Our ex vivo characterization of tumor and adjacent colon cell suspensions suggest that contrasting environments in these tissues promoted inversed expression of T cell co-stimulatory CD80, and co-inhibitory programmed death (PD)-ligand1 (PD-L1) on intratumoral vs. colonic APCs. While putative tumor-specific CD103+CD39+CD8+ TILs expressed lower CD69 (early activation marker) and higher PD-1 (extended activation/exhaustion marker) than colonic counterparts, the latter had instead higher CD69 and lower PD-1 levels. Functional comparisons showed that intratumoral APCs were inferior to colonic APCs regarding protein uptake and upregulation of CD80 and PD-L1 after protein degradation. Our attempt to model CRC treatment-induced T cell activation in vitro showed less interferon (IFN)-γ production by TILs than colonic T cells. In this model, we also measured APCs’ CD80 and PD-L1 expression in response to activated co-residing T cells. These markers were comparable in the two tissues, despite higher IFN- γ exposure for colonic APCs. Thus, APCs within distinct intratumoral and colonic milieus showed different activation and functional status, but were similarly responsive to signals from induced T cell activation.https://www.mdpi.com/2072-6694/13/20/5247colorectal cancertumor microenvironmentantigen presenting cellsT cells |
| spellingShingle | Frank Liang Azar Rezapour Louis Szeponik Samuel Alsén Yvonne Wettergren Elinor Bexe Lindskog Marianne Quiding-Järbrink Ulf Yrlid Antigen Presenting Cells from Tumor and Colon of Colorectal Cancer Patients Are Distinct in Activation and Functional Status, but Comparably Responsive to Activated T Cells Cancers colorectal cancer tumor microenvironment antigen presenting cells T cells |
| title | Antigen Presenting Cells from Tumor and Colon of Colorectal Cancer Patients Are Distinct in Activation and Functional Status, but Comparably Responsive to Activated T Cells |
| title_full | Antigen Presenting Cells from Tumor and Colon of Colorectal Cancer Patients Are Distinct in Activation and Functional Status, but Comparably Responsive to Activated T Cells |
| title_fullStr | Antigen Presenting Cells from Tumor and Colon of Colorectal Cancer Patients Are Distinct in Activation and Functional Status, but Comparably Responsive to Activated T Cells |
| title_full_unstemmed | Antigen Presenting Cells from Tumor and Colon of Colorectal Cancer Patients Are Distinct in Activation and Functional Status, but Comparably Responsive to Activated T Cells |
| title_short | Antigen Presenting Cells from Tumor and Colon of Colorectal Cancer Patients Are Distinct in Activation and Functional Status, but Comparably Responsive to Activated T Cells |
| title_sort | antigen presenting cells from tumor and colon of colorectal cancer patients are distinct in activation and functional status but comparably responsive to activated t cells |
| topic | colorectal cancer tumor microenvironment antigen presenting cells T cells |
| url | https://www.mdpi.com/2072-6694/13/20/5247 |
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