Disruptions in antigen processing and presentation machinery on sarcoma.

Humans Sarcoma / immunology Antigen Presentation / immunology Male Female Middle Aged Aged Adult Antigens, Neoplasm / immunology Proteasome Endopeptidase Complex / metabolism beta 2-Microglobulin / metabolism Prognosis ATP Binding Cassette Transporter, Subfamily B, Member 3
Antigen Processing Machinery Distant Metastasis HLA Class I Personalized Therapy Sarcoma

Journal

Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732

Informations de publication

Date de publication:
09 Sep 2024
Historique:
received: 07 06 2024
accepted: 28 08 2024
medline: 9 9 2024
pubmed: 9 9 2024
entrez: 9 9 2024
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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.

Identifiants

DOI: 10.1007/s00262-024-03822-2 PMID: 39249578
pubmed: 39249578
doi: 10.1007/s00262-024-03822-2
pii: 10.1007/s00262-024-03822-2
doi:

Substances chimiques

Antigens, Neoplasm 0
Proteasome Endopeptidase Complex EC 3.4.25.1
beta 2-Microglobulin 0
TAP2 protein, human 145892-13-3
ATP Binding Cassette Transporter, Subfamily B, Member 3 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

228

Subventions

Organisme : Ministero della Salute
ID : GR-2021-12373209
Organisme : Ministero della Salute
ID : GR-2021-12373209

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Salvatore Lorenzo 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.
ORCID: 0000-0002-0186-1318

Laura Sama' (L)

Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.

Sonia 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.

Omer Mintemur (O)

Pathology Department, IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy.

Laura Ruspi (L)

Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.

Ilaria Santori (I)

Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.

Federico Sicoli (F)

Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.

Alexia Bertuzzi (A)

Oncology Department, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.

Alice Laffi (A)

Oncology Department, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.

Arturo 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.

Piergiuseppe 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.

Vittoria D'amato (V)

Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.

Alessandra 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.

Marta 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.

Luigi 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.

Pierina Navarria (P)

Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.

Maurizio 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.

Vittorio Quagliuolo (V)

Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.

Fabio 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.

Fabio 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.

Ferdinando Carlo Maria 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.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Disruptions in antigen processing and...
Recherchemedicale.com › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu conjonctif et des tissus mous › Sarcomes › Disruptions in antigen processing and...
Recherchemedicale.com › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité cellulaire › Présentation d'antigène › Disruptions in antigen processing and...
Recherchemedicale.com › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Disruptions in antigen processing and...
Recherchemedicale.com › Personnes › Tranches d'âge › Adulte › Sujet âgé › Disruptions in antigen processing and...
Recherchemedicale.com › Personnes › Tranches d'âge › Adulte › Disruptions in antigen processing and...
Recherchemedicale.com › Facteurs biologiques › Antigènes › Antigènes néoplasiques › Disruptions in antigen processing and...
Recherchemedicale.com › Enzymes et coenzymes › Enzymes › Complexes multienzymatiques › Proteasome endopeptidase complex › Disruptions in antigen processing and...
Recherchemedicale.com › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes d'histocompatibilité de classe I › bêta-2-Microglobuline › Disruptions in antigen processing and...
Recherchemedicale.com › Diagnostic › Pronostic › Disruptions in antigen processing and...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Transporteurs d'anions organiques ATP-dépendants › Sous-famille B de transporteurs à cassette liant l'ATP › Transporteur-2 d'antigènes peptidiques › Disruptions in antigen processing and...