AUTHOR=Liu Yujun , Wang Ke , Zhou Yanli , Zhuang Xibing , Shao Shali , Qiao Fulu , Wang Xiangdong , Zou Xin , Qiao Tiankui 

TITLE=Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1039145

DOI=10.3389/fonc.2022.1039145

ISSN=2234-943X

ABSTRACT=Whole-cell tumor vaccines tend to suffer from low immunogenicity. Our previous study showed that irradiated lung cancer cell vaccines in mouse models enhance antitumor efficacy by eliciting an intensive T-cell response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, ATHENA (Autologous Tumor Holo antigEn immuNe Activation). In this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA and profile the immune response by single-cell RNA sequencing (scRNA-seq). After 6 cycles of therapy, PET/CT showed the complete disappearance of liver metastases and the nodal reduction of lung metastases. To investigate the mechanisms of ATHENA, scRNA-seq analyses on PBMCs (peripheral blood mononuclear cells) were applied, which showed that exhausted T cells, including CD8+ T or CD4+ T cells, shifted towards the central memory phenotype after the treatment. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell transitions represent the recovery of antitumoral T cell activity. Taken together, such preliminary studies show that ATHENA therapy may be a promising alternative treatment for tumor patients.