2. Academic Validation
  3. ATP11B triggers the infiltration of T cells into GBM and intensifies anti-GBM immunity by upregulating and externalizing S1PR1

ATP11B triggers the infiltration of T cells into GBM and intensifies anti-GBM immunity by upregulating and externalizing S1PR1

  • J Transl Med. 2025 May 27;23(1):595. doi: 10.1186/s12967-025-06594-0.
Hui Qiu # 1 2,  Ziqin Chen # 1 3,  Jie Chen # 1 2,  Huijuan Yu 3,  Xin Wen 1 2,  Chang Xu 1,  Gongzhen Liu 1,  Luyijie Chai 1,  Longzhen Zhang 1 2,  Yilong Guo 4 5,  Xin Ding 6 7
Affiliations

Affiliations

  • 1 Cancer Institute, Xuzhou Medical University, Jiangsu, Xuzhou, 221000, China.
  • 2 Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China.
  • 3 Department of Radiation Oncology, Affiliated Huai'an Hospital of Yangzhou University, Huai'an Fifth People's Hospital, Huai'an, 223300, Jiangsu, China.
  • 4 Cancer Institute, Xuzhou Medical University, Jiangsu, Xuzhou, 221000, China. guoyilong888@163.com.
  • 5 Department of Radiation Oncology, Affiliated Pizhou Hospital of Xuzhou Medical University, Xuzhou, 221300, Jiangsu, China. guoyilong888@163.com.
  • 6 Cancer Institute, Xuzhou Medical University, Jiangsu, Xuzhou, 221000, China. dingxin81@163.com.
  • 7 Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China. dingxin81@163.com.
  • # Contributed equally.
PMID: 40426254 DOI: 10.1186/s12967-025-06594-0
Abstract

Background: Insufficient T-cell infiltration in tumours causes immune checkpoint inhibitor (ICI) resistance in glioblastoma (GBM) patients. The aim of this study was to demonstrate a preferable way to facilitate T-cell infiltration and improve the therapeutic effects of ICIs in GBM.

Methods: Flow cytometry, western blot and immunofluorescence staining were used to detect the effects of ATP11B upregulation on S1PR1 expression and distribution, T-cell infiltration and differentiation. A coculture system and an intracranial GBM model were established to explore the anti-GBM potential of ATP11B/S1PR1 signaling through systemic administration of CD3-DSPE-PEG2K-NHS/ATP11B nanoparticles to specifically deliver ATP11B overexpressing plasmids to T cells.

Results: S1PR1 deficiency in T cells caused T-cell lymphopenia and systemic immunosuppression in GBM, whereas ATP11B overexpression induced the upregulation and externalization of S1PR1 on T-cell membranes, thus increasing the ability of T cells to eliminate GBM cells. In intracranial GBM models, an ATP11B overexpression plasmid was specifically delivered to T cells in the peripheral blood, bone marrow and spleen, then triggering the infiltration of T cells deeply into the GBM and reversing systemic immunosuppression, ultimately enhancing the therapeutic outcomes of ICIs.

Conclusions: The upregulation and externalization of S1PR1 on T cells mediated by ATP11B overexpression may be promising immunotherapeutic alternatives for GBM treatment.

Keywords

ATP11B; Glioblastoma; Immune checkpoint inhibitor resistance; S1PR1; T-cell lymphopenia.

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