Open Access

ORIGINAL ARTICLE

GM-CSF-producing lymphocytes in tumor-draining lymph nodes of patients with bladder cancer

Ali Ariafar^1,2,a, Mohammadrasul Zareinejad^3,4,a, Mohammadreza Soltani¹, Yasmin Vahidi³, Zahra Faghih³

1 Department of Urology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2 Urology-Oncology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3 Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
4 Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
a These authors had the same contribution to the study

* Corresponding Author: Zahra Faghih,

European Cytokine Network 2021, 32(1), 1-7. https://doi.org/10.1684/ecn.2021.0462

Accepted 13 February 2021;

Abstract

Background: Bladder cancer (BC) is the tenth common cancer worldwide. Despite progress in treatment and the use of chemotherapeutic drugs, the survival rate of BC patients is still low. Manipulation of the immune system was recently introduced as an interesting alternative treatment for this immunogenic cancer with fewer side effects. Accordingly, in the present study, we assessed the frequency of GM-CSF-producing lymphocytes in tumor-draining lymph nodes (TDLNs) of BC patients and evaluated their relationship with clinicopathological factors and survival rate. Methods: Fifty-four patients with BC who had received no treatment were recruited. Mononuclear cells were isolated from fresh homogenized lymph nodes by centrifugation over Ficoll-Hypaque, activated and subsequently analyzed by flow cytometry for the cell surface expression of CD4 and CD8 and the intracellular production of GM-CSF. Results: Flow cytometric analysis revealed that 4.97 ± 2.7% of lymphocytes in TDLNs of patients with BC produced GM-CSF. The mean frequency of GM-CSF-producing cells was 5.5% among CD4⁺ lymphocytes and 11.7% in the CD8⁺ population. Elevated frequencies of GM-CSF-producing lymphocytes, as well as a higher production of GM-CSF by CD4⁺ lymphocytes was observed in the patients with tumor-free lymph nodes, as compared to those with at least one tumor-infiltrated lymph node (p < 0.05). On the other hand, the lower frequency of GM-CSF-producing CD4⁺ lymphocytes (ThGM) was associated with improved overall, but not one-year, survival. No other significant relationship was observed between clinicopathological parameters and the frequency of GM-CSF-producing subsets. Conclusion: Collectively, our findings suggest a protective role for GM-CSF in the early stages of BC; however, the unfavorable association of ThGM frequency with survival rate may imply a more complex role for this cytokine in BC.

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