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Expression of VISTA on tumor-infiltrating immune cells correlated with short intravesical recurrence in non-muscle-invasive bladder cancer

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Abstract

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint molecule expressed in hematopoietic cells, granulocytes, macrophages, and monocytes. However, few studies to date have investigated VISTA expression, especially its clinical utility, in bladder cancer. The present retrospective study aimed to examine VISTA, programmed death ligand-1 (PD-L1), and CD45 expression by immunohistochemical and immunofluorescence staining of archived pathological tissue samples from 159 patients with primary bladder cancer. The correlation between VISTA expression in immune cells (ICs) and clinicopathologic variables including PD-L1 expression in ICs was examined. Briefly, the rates of VISTA-positive ICs and VISTA-positive tumor cells were 67.9% (108/159) and 30.8% (49/159), respectively. The VISTA expression in ICs of patients with bladder cancer, including those with non-muscle-invasive bladder cancer (NMIBC), was positively correlated with tumor stage, grade, size, and multiplicity. The VISTA expression in ICs was stronger in bladder cancer cases with PD-L1-positive ICs than in those with PD-L1-negative ICs (p < 0.001). The mean intravesical recurrence-free survival was shorter in NMIBC cases with VISTA-positive ICs than in those with VISTA-negative ICs (34.0 vs 39.9 months, p = 0.03, log-rank test). In this first study to investigate VISTA expression in bladder cancer, these results implicate VISTA as a potential immunotherapeutic target and immunologic biomarker in bladder cancer.

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Abbreviations

AJCC:

American Joint Committee on Cancer

BCG:

Bacillus Calmette-Guérin

CI:

Confidence interval

ICs:

Immune cells

IVR:

Intravesical recurrence

MIBC:

Muscle-invasive bladder cancer

NMIBC:

Non-muscle-invasive bladder cancer

PD-1:

Programmed cell death protein-1

PD-L1:

Programmed death ligand-1

TCs:

Tumor cells

TMA:

Tissue microarray

VISTA:

V-domain Ig suppressor of T cell activation

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Acknowledgements

The biospecimens used in this study were provided by the Inje Biobank of Inje University Busan Paik Hospital, a member of Korea Biobank Network. And this work was supported by 2018 Inje University Busan Paik Hospital research grant.

Funding

This work was supported by 2018 Inje University Busan Paik Hospital research grant.

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Authors and Affiliations

  1. Department of Urology, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea

    Won Ik Seo, Chan Ho Lee, Wansuk Kim & Jae Il Chung

  2. Department of Pathology, Busan Paik Hospital, Inje University College of Medicine, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Republic of Korea

    Soo Jin Jung & Ha Young Park

  3. Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea

    Dae Sim Lee & Dae Hoon Jeong

  4. Paik Institute of Clinical Research, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea

    Dae Sim Lee & Dae Hoon Jeong

  5. Department of Microbiology and Immunology, Innovative Therapeutics Research Institute, Inje University College of Medicine, Busan, Korea

    Inhak Choi

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  1. Won Ik Seo
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Contributions

WIS: conception, writing and original manuscript preparation, CHL, WK, DSL: data collection and analysis, HYP: funding acquisition, SJJ: acquisition and interpretation of data, re-writing and editing the manuscript, JIJ, DHJ, IC, HYP: conception and design. All authors have commented on previous versions of manuscript and read and approved the final manuscript.

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Correspondence to Soo Jin Jung.

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This study was approved by the Busan Paik Hospital Institutional Review Board (IRB No.17-0195) and was in compliance with ethical guidelines according to the Declaration of Helsinki.

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Informed consent was waived by the Busan Paik Hospital Institutional Review Board on the grounds of being a retrospective study using tumor tissue already archived by the Inje Biobank.

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Seo, W.I., Lee, C.H., Jung, S.J. et al. Expression of VISTA on tumor-infiltrating immune cells correlated with short intravesical recurrence in non-muscle-invasive bladder cancer. Cancer Immunol Immunother 70, 3113–3122 (2021). https://doi.org/10.1007/s00262-021-02906-7

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