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Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer

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Abstract

Purpose

To explore the immune phenotype of peripheral blood mononuclear cells (PBMC) in patients with high-risk non-muscle invasive bladder cancer (NMIBC).

Methods

We prospectively collected blood samples from patients with high-risk NMIBC treated at our institution. PBMC were analyzed by flow cytometry to determine the frequency of T cells and NK cells and the expression of immunoregulatory molecules (Tim-3, TIGIT and PD-1). PBMC from healthy donors (HD) were included for comparison, and associations with response to BCG were investigated.

Results

A total of 38 patients were included, 19 BCG responders and 19 BCG refractory. Compared to 16 PBMC from HD, the frequency of total NK cells was significantly higher in patients with NMIBC [15.2% (IQR: 11.4, 22.2) vs. 5.72% (IQR: 4.84, 9.79); p = 0.05], whereas the frequency of T cells was not statistically different. Both Tim-3 and TIGIT expressions were significantly higher in NMIBC compared to HD, particularly in NK cells [13.8% (11.0; 22.4) vs. 5.56% (4.20; 10.2) and 34.9% (18.9; 53.5) vs. 1.82% (0.63; 5.16), respectively; p < 0.001]. Overall, the expression of PD-1 in all cell types was low in both NMIBC patients and HD. The immune phenotype was not significantly different before and after initiation of BCG. However, the proportion of CD8+ T cells before BCG was significantly higher in responders.

Conclusion

The immune phenotype of PBMC from patients with high-risk NMIBC was significantly different from HD, regardless of the presence of disease or the initiation of BCG. Peripheral CD8+ T cells could play a role in response to BCG.

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Funding

These studies were funded by grants from the Cancer Research Institute and from the National Institutes of Health (R01 CA201189).

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Authors and Affiliations

  1. Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    François Audenet, Harry Anastos & John P. Sfakianos

  2. Division of Hematology and Oncology, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Adam M. Farkas, Matthew D. Galsky & Nina Bhardwaj

Authors
  1. François Audenet
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  2. Adam M. Farkas
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  3. Harry Anastos
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  4. Matthew D. Galsky
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  6. John P. Sfakianos
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Contributions

FA: project development, data collection, data analysis, manuscript writing. AMF: project development, data collection, data analysis, manuscript editing. HA: data collection, manuscript editing. MDG: project development, data analysis, manuscript editing. NB: project development, data analysis, manuscript editing. JPS: project development, data collection, data analysis, manuscript editing

Corresponding author

Correspondence to John P. Sfakianos.

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Conflict of interest

NB is supported by the Parker Institute for Cancer Immunotherapy. AMF is supported by an NIH Immunology Training Grant (T32AI007605).

Research involving human participants

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Audenet, F., Farkas, A.M., Anastos, H. et al. Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer. World J Urol 36, 1741–1748 (2018). https://doi.org/10.1007/s00345-018-2359-7

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  • DOI: https://doi.org/10.1007/s00345-018-2359-7

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