Autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor-associated antigens with diagnostic and prognostic significance
Alveolar rhabdomyosarcoma (ARMS) is a highly aggressive subtype of childhood cancer for which efficacious treatments are needed. Immunotherapy represents a new therapeutic opportunity to pursue, but it requires the identification of worthwhile tumor antigens. Herein, we exploited the capacity of ARM...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2021.1954765 |
| _version_ | 1798034062389018624 |
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| author | Elena Poli Manuela Cattelan Ilaria Zanetti Angela Scagnellato Giuseppe Giordano Angelica Zin Gianni Bisogno Paolo Bonvini |
| author_facet | Elena Poli Manuela Cattelan Ilaria Zanetti Angela Scagnellato Giuseppe Giordano Angelica Zin Gianni Bisogno Paolo Bonvini |
| author_sort | Elena Poli |
| collection | DOAJ |
| description | Alveolar rhabdomyosarcoma (ARMS) is a highly aggressive subtype of childhood cancer for which efficacious treatments are needed. Immunotherapy represents a new therapeutic opportunity to pursue, but it requires the identification of worthwhile tumor antigens. Herein, we exploited the capacity of ARMS autoantibodies to recognize tumor self-antigens, probing human protein microarrays with plasma from ARMS patients and healthy subjects. We assessed the autoantibody response in ARMS, validated data with independent techniques, and estimated autoantibodies diagnostic and prognostic significance by receiver-operator characteristic curves (ROC), uni- and multivariate analysis. Of the 48 tumor antigens identified, General Transcription Factor II–I (GTF2i) and Protocadherin Gamma Subfamily C5 (PCDHGC5) were selected as candidate targets to validate tumor-restricted antigen expression and autoantibody reactivity through an independent technique and wider cohort of cases. GTF2i and PCDHGC5 overexpression was observed in tumor tissues compared to normal counterparts, and anti-GTF2i and -PCDHGC5 autoantibodies were found able to distinguish ARMS patients from healthy subjects as well as cases with different histology. Moreover, low levels of PCDHGC5 autoantibodies characterized patients with worse event-free survival and proved to be an independent negative prognostic factor. This approach provided the first comprehensive autoantibody profile of ARMS, gave novel insights into the immune response of this malignancy and paved the way toward novel potential antibody-based therapeutic applications suitable to improve the survival of ARMS patients. |
| first_indexed | 2024-04-11T20:38:57Z |
| format | Article |
| id | doaj.art-7dcf67de8c3c41d6a830ea3218bcb1a0 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-04-11T20:38:57Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-7dcf67de8c3c41d6a830ea3218bcb1a02022-12-22T04:04:17ZengTaylor & Francis GroupOncoImmunology2162-402X2021-01-0110110.1080/2162402X.2021.19547651954765Autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor-associated antigens with diagnostic and prognostic significanceElena Poli0Manuela Cattelan1Ilaria Zanetti2Angela Scagnellato3Giuseppe Giordano4Angelica Zin5Gianni Bisogno6Paolo Bonvini7University of PaduaUniversity of PaduaUniversity of PaduaUniversity of PaduaUniversity of PaduaFondazione Città Della SperanzaUniversity of PaduaFondazione Città Della SperanzaAlveolar rhabdomyosarcoma (ARMS) is a highly aggressive subtype of childhood cancer for which efficacious treatments are needed. Immunotherapy represents a new therapeutic opportunity to pursue, but it requires the identification of worthwhile tumor antigens. Herein, we exploited the capacity of ARMS autoantibodies to recognize tumor self-antigens, probing human protein microarrays with plasma from ARMS patients and healthy subjects. We assessed the autoantibody response in ARMS, validated data with independent techniques, and estimated autoantibodies diagnostic and prognostic significance by receiver-operator characteristic curves (ROC), uni- and multivariate analysis. Of the 48 tumor antigens identified, General Transcription Factor II–I (GTF2i) and Protocadherin Gamma Subfamily C5 (PCDHGC5) were selected as candidate targets to validate tumor-restricted antigen expression and autoantibody reactivity through an independent technique and wider cohort of cases. GTF2i and PCDHGC5 overexpression was observed in tumor tissues compared to normal counterparts, and anti-GTF2i and -PCDHGC5 autoantibodies were found able to distinguish ARMS patients from healthy subjects as well as cases with different histology. Moreover, low levels of PCDHGC5 autoantibodies characterized patients with worse event-free survival and proved to be an independent negative prognostic factor. This approach provided the first comprehensive autoantibody profile of ARMS, gave novel insights into the immune response of this malignancy and paved the way toward novel potential antibody-based therapeutic applications suitable to improve the survival of ARMS patients.http://dx.doi.org/10.1080/2162402X.2021.1954765alveolar rhabdomyosarcomaprotein microarraytumor-associated antigenscancer autoantibodiesdiagnostic and prognostic factors |
| spellingShingle | Elena Poli Manuela Cattelan Ilaria Zanetti Angela Scagnellato Giuseppe Giordano Angelica Zin Gianni Bisogno Paolo Bonvini Autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor-associated antigens with diagnostic and prognostic significance OncoImmunology alveolar rhabdomyosarcoma protein microarray tumor-associated antigens cancer autoantibodies diagnostic and prognostic factors |
| title | Autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor-associated antigens with diagnostic and prognostic significance |
| title_full | Autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor-associated antigens with diagnostic and prognostic significance |
| title_fullStr | Autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor-associated antigens with diagnostic and prognostic significance |
| title_full_unstemmed | Autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor-associated antigens with diagnostic and prognostic significance |
| title_short | Autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor-associated antigens with diagnostic and prognostic significance |
| title_sort | autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor associated antigens with diagnostic and prognostic significance |
| topic | alveolar rhabdomyosarcoma protein microarray tumor-associated antigens cancer autoantibodies diagnostic and prognostic factors |
| url | http://dx.doi.org/10.1080/2162402X.2021.1954765 |
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