Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes
Introduction Local T-cell immunity is recognized for its contribution to the evolution and therapy response of various carcinomas. Here, we investigated characteristics of tumor-infiltrating lymphocytes (TILs), as well as T-cell evasive mechanisms in different soft tissue sarcoma (STS) subtypes.Meth...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2020-10-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e000271.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849221765876678656 |
|---|---|
| author | Cornelis Verhoef Reno Debets Yarne Klaver Stefan Sleijfer Dirk Grünhagen Rebecca Wijers Maud Rijnders Astrid Oostvogels Marcel Smid Cor Lamers |
| author_facet | Cornelis Verhoef Reno Debets Yarne Klaver Stefan Sleijfer Dirk Grünhagen Rebecca Wijers Maud Rijnders Astrid Oostvogels Marcel Smid Cor Lamers |
| author_sort | Cornelis Verhoef |
| collection | DOAJ |
| description | Introduction Local T-cell immunity is recognized for its contribution to the evolution and therapy response of various carcinomas. Here, we investigated characteristics of tumor-infiltrating lymphocytes (TILs), as well as T-cell evasive mechanisms in different soft tissue sarcoma (STS) subtypes.Methods Liposarcoma, gastrointestinal stromal tumor (GIST), leiomyosarcoma, myxofibrosarcoma and pleomorphic sarcomas were assessed for T-cell numbers and phenotypes using flow cytometry. Next-generation sequencing was used to analyze T-cell receptor repertoire, mutational load, immune cell frequencies, and expression of immune-related genes.Results GIST, myxofibrosarcoma and pleomorphic sarcoma showed high numbers of CD8+ TILs, with GIST having the lowest fraction of effector memory T cells. These TILs coexpress the immune checkpoints PD1, TIM3, and LAG3 in myxofibrosarcoma and pleomorphic sarcoma, yet TILs coexpressing these checkpoints were near negligible in GIST. Fractions of dominant T-cell clones among STS subtypes were lowest in GIST and liposarcoma, whereas mutational load was relatively low in all STS subtypes. Furthermore, myeloid-derived cells and expression of the costimulatory ligands CD86, ICOS-L and 41BB-L were lowest in GIST when compared with other STS subtypes.Conclusion STS subtypes differ with respect to number and phenotypical signs of antitumor responsiveness of CD8+ TILs. Notably, GIST, myxofibrosarcoma and pleomorphic sarcoma harbor high numbers of CD8+ T cells, yet in the GIST microenvironment, these T cells are less differentiated and non-exhausted, which is accompanied with a relatively low expression of costimulatory ligands. |
| format | Article |
| id | doaj-art-ec571a33f8794e5489b382fe799a0bba |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-ec571a33f8794e5489b382fe799a0bba2024-11-10T18:45:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2019-000271Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypesCornelis Verhoef0Reno Debets1Yarne Klaver2Stefan Sleijfer3Dirk Grünhagen4Rebecca Wijers5Maud Rijnders6Astrid Oostvogels7Marcel Smid8Cor Lamers9Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC, Rotterdam, The NetherlandsLaboratory of Tumor Immunology, Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The NetherlandsAff1 000000040459992Xgrid.5645.2Laboratory of Tumor Immunology, Department of Medical OncologyErasmus MC Cancer Institute Office Be 430b, Wytemaweg 80 3015 Rotterdam CN The Netherlands2 Medical Oncology, Erasmus MC, Rotterdam, Zuid-Holland, The NetherlandsDepartment of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC, Rotterdam, The Netherlands2Erasmus MC Cancer Institute, Rotterdam, Netherlands1 Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC, Rotterdam, The Netherlands1 Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC, Rotterdam, The Netherlands2 Medical Oncology, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands1 Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC, Rotterdam, The NetherlandsIntroduction Local T-cell immunity is recognized for its contribution to the evolution and therapy response of various carcinomas. Here, we investigated characteristics of tumor-infiltrating lymphocytes (TILs), as well as T-cell evasive mechanisms in different soft tissue sarcoma (STS) subtypes.Methods Liposarcoma, gastrointestinal stromal tumor (GIST), leiomyosarcoma, myxofibrosarcoma and pleomorphic sarcomas were assessed for T-cell numbers and phenotypes using flow cytometry. Next-generation sequencing was used to analyze T-cell receptor repertoire, mutational load, immune cell frequencies, and expression of immune-related genes.Results GIST, myxofibrosarcoma and pleomorphic sarcoma showed high numbers of CD8+ TILs, with GIST having the lowest fraction of effector memory T cells. These TILs coexpress the immune checkpoints PD1, TIM3, and LAG3 in myxofibrosarcoma and pleomorphic sarcoma, yet TILs coexpressing these checkpoints were near negligible in GIST. Fractions of dominant T-cell clones among STS subtypes were lowest in GIST and liposarcoma, whereas mutational load was relatively low in all STS subtypes. Furthermore, myeloid-derived cells and expression of the costimulatory ligands CD86, ICOS-L and 41BB-L were lowest in GIST when compared with other STS subtypes.Conclusion STS subtypes differ with respect to number and phenotypical signs of antitumor responsiveness of CD8+ TILs. Notably, GIST, myxofibrosarcoma and pleomorphic sarcoma harbor high numbers of CD8+ T cells, yet in the GIST microenvironment, these T cells are less differentiated and non-exhausted, which is accompanied with a relatively low expression of costimulatory ligands.https://jitc.bmj.com/content/8/2/e000271.full |
| spellingShingle | Cornelis Verhoef Reno Debets Yarne Klaver Stefan Sleijfer Dirk Grünhagen Rebecca Wijers Maud Rijnders Astrid Oostvogels Marcel Smid Cor Lamers Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes Journal for ImmunoTherapy of Cancer |
| title | Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes |
| title_full | Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes |
| title_fullStr | Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes |
| title_full_unstemmed | Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes |
| title_short | Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes |
| title_sort | differential quantities of immune checkpoint expressing cd8 t cells in soft tissue sarcoma subtypes |
| url | https://jitc.bmj.com/content/8/2/e000271.full |
| work_keys_str_mv | AT cornelisverhoef differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes AT renodebets differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes AT yarneklaver differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes AT stefansleijfer differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes AT dirkgrunhagen differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes AT rebeccawijers differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes AT maudrijnders differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes AT astridoostvogels differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes AT marcelsmid differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes AT corlamers differentialquantitiesofimmunecheckpointexpressingcd8tcellsinsofttissuesarcomasubtypes |