Sarcoma Common MHC-I Haplotype Restricts Tumor-Specific CD8+ T Cell Response
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Cell Cultures
2.2. DNA/RNA Isolation and cDNA Synthesis
2.3. HLA Genotyping
2.4. Western Blots
2.5. Complement-Dependent Cytotoxicity Assay
2.6. Immunohistochemistry
2.7. Preparation of CD8+ Lymphocytes and FACS Analysis
2.8. T Cell Division Cycle Profile by CFSE
2.9. Tissue Specimen Cultures
2.10. CD8 T Cell Cytotoxicity Assay
2.11. Determination of T Cell-Mediated Cell Killing by FACS
2.12. Statistical Analysis
3. Results
3.1. HLA-I Genotype in Sarcoma Tissues
3.2. Expression of HLA-I Antigens in Sarcoma Tissues
3.3. PD-L1 Expression in Sarcoma Biopsies
3.4. Patient’s T Cells Characterization
3.5. Characterization of HLA-A24* and PD-L1 Antigens in Selected Biopsies
3.6. Immune Sensitivity of HLA-A24* Tumors to Cytotoxicity Mediated by TCR
3.7. Reactivity of T Cell against HLA-A24 Restricted Antigen
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patients | 40 |
---|---|
Diagnosis | |
Myxoid liposarcoma (MLPS) | 6 |
Undifferentiated sarcoma (UDS) | 10 |
Undifferentiated Pleomorphic sarcoma (UPS) | 6 |
Leiomyosarcoma (LMS) | 6 |
Myxofibrosarcoma (MFS) | 12 |
Age yrs | 65 ± 1 |
Gender | |
Male | 16 |
Female | 24 |
Localization | |
Upper extremities | 12 |
Lower extremities | 20 |
Trunk | 8 |
Stage (AJCC system) | |
I | 12 |
II | 5 |
III | 20 |
Recurrence | 3 |
Surgery | 40 |
Radiotherapy | |
No | 36 |
Adjuvant | 4 |
Tumor size | |
≥5 cm | 18 |
≤5 cm | 22 |
Residual disease after surgery | |
R0 | 33 |
R1/R2 | 7 |
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Mosca, L.; de Angelis, A.; Ronchi, A.; De Chiara, A.; Fazioli, F.; Ruosi, C.; Altucci, L.; Conte, M.; de Nigris, F. Sarcoma Common MHC-I Haplotype Restricts Tumor-Specific CD8+ T Cell Response. Cancers 2022, 14, 3414. https://doi.org/10.3390/cancers14143414
Mosca L, de Angelis A, Ronchi A, De Chiara A, Fazioli F, Ruosi C, Altucci L, Conte M, de Nigris F. Sarcoma Common MHC-I Haplotype Restricts Tumor-Specific CD8+ T Cell Response. Cancers. 2022; 14(14):3414. https://doi.org/10.3390/cancers14143414
Chicago/Turabian StyleMosca, Laura, Alessandra de Angelis, Andrea Ronchi, Annarosaria De Chiara, Flavio Fazioli, Carlo Ruosi, Lucia Altucci, Mariarosaria Conte, and Filomena de Nigris. 2022. "Sarcoma Common MHC-I Haplotype Restricts Tumor-Specific CD8+ T Cell Response" Cancers 14, no. 14: 3414. https://doi.org/10.3390/cancers14143414