Granulocyte Colony-Stimulating Factor-Producing Bladder Cancer

Morinaga, Ryota; Kawahara, Takashi; Kuroda, Shinnosuke; Inayama, Yoshiaki; Uemura, Hiroji

doi:10.1159/000502174

Cited by 6 publications

(3 citation statements)

References 6 publications

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“…Several studies have documented cross talk between cancer and immune cells, but also inflammatory factors that are expressed by the TME, such as the CSF family of cytokines, which attract macrophages (through CCL2 and VEGFA) [ 29 , 30 , 31 , 32 ]. We have shown that G-CSF is highly expressed in GI cancers [ 17 , 33 ] and is associated with tumor progression and poor prognosis in several other cancer types, such as prostate [ 34 ], neuroblastoma [ 35 ], bladder [ 36 ], non-small cell lung cancer [ 37 ], and head and neck squamous cell carcinomas [ 38 ]. However, little is known regarding the role of the G-CSF in the TME, particularly related to immune cells.…”

Section: Discussionmentioning

confidence: 99%

G-CSF and G-CSFR Induce a Pro-Tumorigenic Macrophage Phenotype to Promote Colon and Pancreas Tumor Growth

Karagiannidis

Vilet

Egal

et al. 2020

Cancers

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Tumor-associated macrophages (TAMs) in the gastrointestinal tumor microenvironment (TME) are known to polarize into populations exhibiting pro- or anti-tumoral activity in response to stimuli such as growth factors and cytokines. Our previous work has recognized granulocyte colony-stimulating factor (G-CSF) as a cytokine capable of influencing immune cells of the TME exhibiting pro-tumoral activity. Here, we aimed to focus on how G-CSF regulates TAM phenotype and function and the effects on gastrointestinal (GI) tumor progression. Thus, wildtype (WT) and G-CSFR−/− macrophages were examined for cytokine production, gene expression, and transcription factor activity. Adoptive transfer of WT or G-CSFR−/− macrophages into tumor-bearing mice was performed to study their influence in the progression of colon (MC38) and pancreatic (PK5L1940) tumor mouse models. Finally, the difference in cytotoxic potential between WT and G-CSFR−/− macrophages was examined both in vitro and in vivo. Our results indicate that G-CSF promotes increased IL-10 production and decreased IL-12 production, which was reversed in G-CSFR−/− macrophages for a pro-inflammatory phenotype. Furthermore, G-CSFR−/− macrophages were characterized by higher levels of NOS2 expression and NO production, which led to greater tumor related cytotoxicity both in vitro and in vivo. Our results suggest that in the absence of G-CSFR, macrophage-related tumor cytotoxicity was amplified. These findings, along with our previous reports, pinpoint G-CSF /G-CSFR as a prominent target for possible clinical applications that aim to control the TME and the GI tumor progression.

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Section: Discussionmentioning

confidence: 99%

G-CSF and G-CSFR Induce a Pro-Tumorigenic Macrophage Phenotype to Promote Colon and Pancreas Tumor Growth

Karagiannidis

Vilet

Egal

et al. 2020

Cancers

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“…These outcomes align with the observations made by Bajorin et al during the pre-immunotherapy era, when cisplatin-based therapy was primarily the established treatment protocol [ 33 ]. Leukocytosis, as indicated in previous reports, may be linked to tumors that produce granulocyte colony-stimulating factor (G-CSF), and this association is correlated with a less favorable prognosis [ 34 ]. Similarly, anemia has been identified as an independent factor associated with reduced OS and CSS among urothelial carcinoma patients [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy

Tsai,

Su,

Huang

et al. 2023

BMC Cancer

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Background While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. Method We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. Result A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). Conclusion The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.

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“…[ 12 ] This condition is rare, although only several case reports have shown leukocytosis in a patient with bladder cancer due to a G-CSF-producing tumor. [ 13 14 15 ] G-CSF has also been associated to tumor cell proliferation which is aggressive and has a poor clinical outcome. [ 15 ] This condition can explain the cause of poor prognosis and short survival in this study.…”

Section: Discussionmentioning

confidence: 99%

Poor prognosis of urothelial carcinoma in patients presented with persistent paraneoplastic leukocytosis with anemia

et al. 2022

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Introduction: Paraneoplastic leukocytosis is a rare manifestation of urological cancer. This condition is well associated with the poor prognosis in other solid tumors. Anemia is the most common hematological manifestation of cancer, affecting 40%–64% of patients with cancer. This condition is also well associated with a poor prognosis. The goal of this research is to determine the clinical presentation and fate of individuals with urothelial carcinoma who have persistent paraneoplastic leukocytosis and anemia. Methods: From January 2014 to December 2020, a retrospective cohort of patients with a histological result of urothelial carcinoma was collected. Data were extracted from a single National Cancer Center Hospital in Indonesia. Persistent leukocytosis is defined as a leukocyte count ≥20,000/mL on at least two occasions with a minimum interval of 30 days. Anemia is defined using the WHO definition of anemia. Urinalysis, chest X-ray, and other blood tests were performed to exclude other probable causes of leukocytosis. Results: Thirteen of 123 patients screened presented with persistent paraneoplastic leukocytosis and anemia. All patients presented with bladder cancer, with two patients (15.4%) presented with a mixed histological urothelial carcinoma. During the trial, all of the patients died, with a median survival of 20 days after the beginning of paraneoplastic leukocytosis with anemia. Conclusions: Persistent paraneoplastic leukocytosis and anemia in a patient with urothelial carcinoma are a rare condition that is associated to a poor prognosis and a lower median overall survival time.

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Granulocyte Colony-Stimulating Factor-Producing Bladder Cancer

Cited by 6 publications

References 6 publications

G-CSF and G-CSFR Induce a Pro-Tumorigenic Macrophage Phenotype to Promote Colon and Pancreas Tumor Growth

G-CSF and G-CSFR Induce a Pro-Tumorigenic Macrophage Phenotype to Promote Colon and Pancreas Tumor Growth

The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy

Poor prognosis of urothelial carcinoma in patients presented with persistent paraneoplastic leukocytosis with anemia

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