Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient
BackgroundWhole-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 cells response and improving immunogenicity. Based on these findings, we developed an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1039145/full |
| _version_ | 1797986904205950976 |
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| author | Yujun Liu Ke Wang Yanli Zhou Xibing Zhuang Shali Shao Fulu Qiao Xiangdong Wang Xin Zou Tiankui Qiao |
| author_facet | Yujun Liu Ke Wang Yanli Zhou Xibing Zhuang Shali Shao Fulu Qiao Xiangdong Wang Xin Zou Tiankui Qiao |
| author_sort | Yujun Liu |
| collection | DOAJ |
| description | BackgroundWhole-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 cells response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, Autologous Tumor Holo antigEn immuNe Activation (ATHENA).MethodsIn this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA. After 6 cycles of therapy, PET/CT showed the therapeutic efficacy of ATHENA. We profiled the immune response by single-cell RNA sequencing (scRNA-seq). Flow cytometry analysis was implemented to validate the status transitions of CD8+ T cells.ResultsIn CD8+ T cells, the exhausted status was weakened after treatment. The exhausted CD4+ T cells shifted towards the central memory phenotype after the treatment. Breg cells were converted to Plasma or Follicular B cells. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell and B cell transitions represent the recovery of antitumoral adaptive immune response. We validated that the proportion of CD279+CD8+ T cells were reduced and the expression of CD44 molecule was upregulated by flow cytometry assay.ConclusionSuch studies not only show that ATHENA therapy may be a promising alternative treatment for tumor patients but provide a novel idea to analyses the mechanisms of rare cases or personalized cancer treatment. |
| first_indexed | 2024-04-11T07:40:28Z |
| format | Article |
| id | doaj.art-24fc8d66f3344b0ea76dbd246247bfaa |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T07:40:28Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-24fc8d66f3344b0ea76dbd246247bfaa2022-12-22T04:36:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10391451039145Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patientYujun Liu0Ke Wang1Yanli Zhou2Xibing Zhuang3Shali Shao4Fulu Qiao5Xiangdong Wang6Xin Zou7Tiankui Qiao8Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, ChinaCenter for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, ChinaNuclear Medicine Department, Jinshan Hospital, Fudan University, Shanghai, ChinaCenter for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, ChinaCenter for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, ChinaDepartment of Breast Surgery, Tai’an Central Hospital, Tai’an, ChinaCenter for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, ChinaCenter for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, ChinaCenter for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, ChinaBackgroundWhole-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 cells response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, Autologous Tumor Holo antigEn immuNe Activation (ATHENA).MethodsIn this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA. After 6 cycles of therapy, PET/CT showed the therapeutic efficacy of ATHENA. We profiled the immune response by single-cell RNA sequencing (scRNA-seq). Flow cytometry analysis was implemented to validate the status transitions of CD8+ T cells.ResultsIn CD8+ T cells, the exhausted status was weakened after treatment. The exhausted CD4+ T cells shifted towards the central memory phenotype after the treatment. Breg cells were converted to Plasma or Follicular B cells. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell and B cell transitions represent the recovery of antitumoral adaptive immune response. We validated that the proportion of CD279+CD8+ T cells were reduced and the expression of CD44 molecule was upregulated by flow cytometry assay.ConclusionSuch studies not only show that ATHENA therapy may be a promising alternative treatment for tumor patients but provide a novel idea to analyses the mechanisms of rare cases or personalized cancer treatment.https://www.frontiersin.org/articles/10.3389/fonc.2022.1039145/fullsingle-cell RNA sequencingautologous tumor vaccinesscSTART cellsB cellsexhausted state |
| spellingShingle | Yujun Liu Ke Wang Yanli Zhou Xibing Zhuang Shali Shao Fulu Qiao Xiangdong Wang Xin Zou Tiankui Qiao Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient Frontiers in Oncology single-cell RNA sequencing autologous tumor vaccines scSTAR T cells B cells exhausted state |
| title | Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient |
| title_full | Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient |
| title_fullStr | Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient |
| title_full_unstemmed | Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient |
| title_short | Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient |
| title_sort | single cell analyses reveal the therapeutic effects of athena and its mechanism in a rhabdomyosarcoma patient |
| topic | single-cell RNA sequencing autologous tumor vaccines scSTAR T cells B cells exhausted state |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1039145/full |
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