Disruptions in antigen processing and presentation machinery on sarcoma.

Autor: Renne SL; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy. salvatore.renne@hunimed.eu.; Pathology Department, IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy. salvatore.renne@hunimed.eu., Sama' L; Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Kumar S; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Mintemur O; Pathology Department, IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy., Ruspi L; Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Santori I; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy., Sicoli F; Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Bertuzzi A; Oncology Department, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Laffi A; Oncology Department, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Bonometti A; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Pathology Department, IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy., Colombo P; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Pathology Department, IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy., D'amato V; Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Bressan A; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Pathology Department, IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy., Scorsetti M; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Terracciano L; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Pathology Department, IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy., Navarria P; Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., D'incalci M; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Cancer Pharmacology Laboratory, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Quagliuolo V; Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Pasqualini F; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Grizzi F; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy., Cananzi FCM; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.; Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2024 Sep 09; Vol. 73 (11), pp. 228. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1007/s00262-024-03822-2
Abstrakt: Background: The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients.
Methods: We investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001-2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used.
Results: All investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS.
Conclusion: Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: