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ma=86400 Temporal dynamics of immune cell patterns in bladder cancer patients receiving Bacillus Calmette-Guérin therapy | British Journal of Cancer
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Clinical Studies

Temporal dynamics of immune cell patterns in bladder cancer patients receiving Bacillus Calmette-Guérin therapy

British Journal of Cancer volume 131, pages 1901–1912 (2024)Cite this article

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Abstract

Background

Bacillus Calmette-Guérin (BCG) is capable of enhancing the infiltration of immune cells into the tumour. However the temporal dynamics of immune cell patterns in patients receiving BCG instillation remains unclear.

Methods

Ninety-six patients who underwent intravesical BCG therapy, comprising 46 responders and 50 non-responders, were retrospectively enroled to explore the evolving immune landscape. This study involved a detailed examination of sequential samples collected before, during, and after BCG treatment to assess BCG’s influence on the immune microenvironment, employing techniques such as immunohistochemistry, fluorescent multiplex immunohistochemistry, and mass spectrometry techniques.

Results

Our study found that initial BCG instillation leads to enhanced immune cell infiltration, correlating with treatment efficacy, with responders exhibiting more pronounced increases. Non-responders experience a rise in immune cell infiltration and PD-L1 expression during the first instillation, which returns to baseline after treatment. In non-responders, BCG re-challenge fail to further increase immune cell infiltration into the tumour or improve patient outcomes. Strikingly, proteomics data revealed that GBP1 expression was induced by BCG treatment in non-responders.

Conclusions

Our findings demonstrated the induction of tumour PD-L1 expression by BCG in non-responders, and therefore provide insights for the combination of BCG and anti-PD1/anti-PD-L1 therapy.

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Fig. 1: Flowchart of the study.
Fig. 2: The difference of immune cell distributions in pre-BCG and on-BCG tissues of responders and non-responders.
Fig. 3: The differences of immune cell patterns between responders and non-responders before and during BCG treatment.
Fig. 4: Temporal dynamics of immune cell infiltration before, during and after BCG treatment in non-responders.
Fig. 5: Dynamic modulation of immune cell patterns mediated by BCG treatment in non-responders.
Fig. 6: BCG re-challenge failed to increase immune infiltration in non-responders.
Fig. 7: Quantitative proteomic analysis of tumour tissues before and during BCG instillation.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD055011.

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Author contributors

Jiang-Li Lu: Wrting-Original Draft, Visualization, Methodology; Yun-Lin Ye: Resource; Dan-Dan Zheng: Methodology; Xin-Yu Shi: Methodology; Li-Ling Hu: Investigation; Xiao-Yi Yuan: Investigation; Tao-Nong Cai: Investigation; Kun Meng: Methodology; Neng-Qiao Wen: Investigation; Yu-Ying Li: Investigation; Ding-Kang Wang: Investigation; Fu-Jin Shi: Investigation; Dan-Ya Liu: Investigation; Qing-Yu He: Resources; Zi-Ke Qin: Resources; Chris Zhiyi Zhang: Writing-Review&Editing, Supervision, Funding acquisition; Yun Cao: Writing-Review&Editing, Project administration, Funding acquisition.

Funding

This work was supported by supported by a grant from the Nature Science Foundation of China (No. 81872085), the National Key Research and Development Programme of China (2022YFA1304604), and the Natural Science Foundation of Guangdong Province (2022A1515012388).

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Author notes

  1. These authors contributed equally: Jiang-Li Lu, Yun-Lin Ye, Dan-Dan Zheng.

Authors and Affiliations

  1. MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China

    Jiang-Li Lu, Dan-Dan Zheng, Xin-Yu Shi, Li-Ling Hu, Xiao-Yi Yuan, Kun Meng, Neng-Qiao Wen, Yu-Ying Li, Fu-Jin Shi, Dan-Ya Liu, Qing-Yu He & Chris Zhiyi Zhang

  2. Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China

    Jiang-Li Lu, Yun-Lin Ye, Tao-Nong Cai & Zi-Ke Qin

  3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China

    Jiang-Li Lu, Yun-Lin Ye, Tao-Nong Cai, Neng-Qiao Wen, Ding-Kang Wang, Zi-Ke Qin & Yun Cao

  4. Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China

    Kun Meng

  5. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China

    Neng-Qiao Wen, Ding-Kang Wang & Yun Cao

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Correspondence to Zi-Ke Qin, Chris Zhiyi Zhang or Yun Cao.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all patients. This study has been approved by the ethics committee of the Sun Yat-sen University Cancer Centre (B2022-201-01).

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Lu, JL., Ye, YL., Zheng, DD. et al. Temporal dynamics of immune cell patterns in bladder cancer patients receiving Bacillus Calmette-Guérin therapy. Br J Cancer 131, 1901–1912 (2024). https://doi.org/10.1038/s41416-024-02883-5

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