AUTHOR=Wang Yi , Li Chunzhao , Chi Xiaohan , Huang Xijian , Gao Hua , Ji Nan , Zhang Yang TITLE=Low MxA Expression Predicts Better Immunotherapeutic Outcomes in Glioblastoma Patients Receiving Heat Shock Protein Peptide Complex 96 Vaccination JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.865779 DOI=10.3389/fonc.2022.865779 ISSN=2234-943X ABSTRACT=
Heat shock protein peptide complex 96 (HSPPC-96) has been proven to be a safe and preliminarily effective therapeutic vaccine in treating newly diagnosed glioblastoma multiforme (GBM) (NCT02122822). However, the clinical outcomes were highly variable, rendering the discovery of outcome-predictive biomarkers essential for this immunotherapy. We utilized multidimensional immunofluorescence staining to detect CD4+ CD8+ and PD-1+ immune cell infiltration levels, MxA and gp96 protein expression in pre-vaccination GBM tissues of 19 patients receiving HSPPC-96 vaccination. We observed low MxA expression was associated with longer OS than high MxA expression (48 months vs. 20 months, p=0.038). Long-term survivors (LTS) exhibited significantly lower MxA expression than short-term survivors (STS) (p= 0.0328), and ROC curve analysis indicated MxA expression as a good indicator in distinguishing LTS and STS (AUC=0.7955, p=0.0318). However, we did not observe any significant impact of immune cell densities or gp96 expression on patient outcomes. Finally, we revealed the association of MxA expression with prognosis linked to a preexisting TCR clone (CDR3-2) but was independent of the peripheral tumor-specific immune response. Taken together, low MxA expression correlated with better survival in GBM patients receiving HSPPC-96 vaccination, indicating MxA as a potential biomarker for early recognition of responsive patients to this immunotherapy.