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.