OK-432 Suppresses Proliferation and Metastasis by Tumor Associated Macrophages in Bladder Cancer

Tian, Yazhou; Tang, Kun; Guan, Wei; Yang, Tao; Xu, Hua; Zhuang, Qianyuan; Ye, Zhangqun

doi:10.7314/apjcp.2015.16.11.4537

Cited by 14 publications

(15 citation statements)

References 28 publications

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“…Furthermore, the optimal dose of intratumoural OK-432 injection is yet to be validated. We used 0.075 KE (0.5 KE/kg) in the present study based on a previous report 34 . As a result, we indicated that the efficacy of OK-432 was approximately equivalent to that of RFA, while various authors had reported that the efficacy of OK-432 was slightly weaker than that of RFA 25,35 .…”

Section: Discussionmentioning

confidence: 99%

Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model

Iwai

Oebisu

Hoshi

et al. 2020

Sci Rep

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Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evaluate overall survival and tumour size: control (no treatment), RFA-only, OK-432, and RFA-OK-432. The remaining 65 were assigned for histological examination. Maximum diameters of tibial and lung tumours were determined. Tumour samples were histologically examined using haematoxylin-eosin and immunohistochemical staining. Overall survival was significantly prolonged in the RFA-OK-432 group compared to the RFA-only and OK-432 groups. Only rats in the RFA-OK-432 group exhibited significant decreases in maximum tumour diameter after treatment. Ki-67-positive tumour cells in the RFA-OK-432 group were significantly stained negative on immunohistochemical analysis as opposed to those in the RFA-only and OK-432 groups. The number of CD11c+, OX-62+, CD4+, and CD8 + cells significantly increased in the RFA-OK-432 group compared to the RFA-only group. RFA with intratumoural OK-432 injection resulted in distant tumour suppression, prolonged survival, and increased dendritic cells, cytotoxic T cells, IFN-γ, and TNF-α, whereas RFA or OK-432 alone did not produce this effect. This combination may induce an abscopal effect in human osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model

Iwai

Oebisu

Hoshi

et al. 2020

Sci Rep

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“…It was demonstrated that EC has an active role in promoting cancer cell proliferation, survival, migration and invasion. A number of previous reports suggested a role for macrophages (26,27) and neutrophils (28) in the progression of bladder cancer. However, the role of ECs in the tumor microenvironment in bladder cancer is only beginning to be unveiled.…”

Section: Discussionmentioning

confidence: 99%

Bladder cancer cells interact with vascular endothelial cells triggering EGFR signals to promote tumor progression

et al. 2019

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Although important progress has been made in elucidating the role of the tumor microenvironment in the development of bladder cancer, little is currently known regarding the interactions with vascular endothelial cells (ECs) that promote cancer progression. In the present study, it is reported that epidermal growth factor receptor ligands induced by the upregulation of vascular endothelial growth factor (VEGF)-A and VEGF-C via the VEGF receptor (R)2/nuclear factor-κB signaling pathway in ECs, may trigger EGFR signaling in bladder cancer cells and promote bladder cancer progression. Furthermore, the interaction between bladder cancer cells and ECs enhanced EC recruitment though the CXCL1/CXCL5/CXCL8-CXCR2 pathway. Western blotting was used to evaluate the presence of VEGFR, EGFR and nuclear factor-κB, and reverse transcription-quantitative polymerase chain reaction was used to evaluate the expression of VEGFR ligands and EGFR ligands. The present results indicate the mechanism by which the indirect interplay between bladder cancer cells and vascular ECs promotes cancer progression, through the VEGFR2 signaling pathway in vascular ECs and through the EGFR signaling pathway in bladder cancer cells.

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“…In our center (Department of Urology, First Affiliated Hospital of Sun Yat-sen University), good results have been achieved in preventing recurrence and progression of NMIBC by administering OK-432 as an intravesical immunotherapeutic agent (22). Previous studies have proposed that the primary antitumor role of OK-432 in bladder carcinoma involves mobilization of the cellular immune system by activating macrophages, NK cells, lymphokine-activated killer cells and various T cells (23,24). Secondary roles include increasing the binding capacity of these cells to the tumor cells, thereby enhancing the antitumor effect (25).…”

Section: Discussionmentioning

confidence: 99%

Effects of programmed death-ligand 1 expression on OK-432 immunotherapy following transurethral resection in non-muscle invasive bladder cancer

et al. 2017

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The present study aimed to investigate the effect of the negative costimulatory molecule programmed death-ligand 1 (PD-L1) on immunotherapy with OK-432, following transurethral resection of bladder tumors in non-muscle invasive bladder cancer (NMIBC), and to elucidate the underlying mechanism. PD-L1 was detected by immunohistochemical staining in tumor specimens from 55 cases of NMIBC following postoperative immunotherapy with OK-432. The PD-L1 mRNA and protein expression levels were measured in the bladder cancer T24 cell line and the human uroepithelial SV-HUC-1 cell line, following treatment with interleukin (IL)-2, interferon (IFN)-α and IFN-γ, by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. PD-L1 was widely expressed in the NMIBC tumors, with 56.4% (31/55) of specimens exhibiting positive staining. When compared with PD-L1-negative patients, PD-L1-positive patients exhibited significantly increased recurrence [48.4% (15/31) vs. 16.7% (4/24)] and progression [16.1% (5/31) vs. 4.2% (1/24)] rates (P<0.05). RT-qPCR and western blotting demonstrated that cytokines IL-2, IFN-α and IFN-γ markedly upregulated PD-L1 mRNA expression rates and protein levels in bladder cancer T24 cells (P<0.05), but had no significant effect in non-tumor SV-HUC-1 cells. In conclusion, PD-L1 expression was negatively-associated with the efficacy of OK-432 intravesical immunotherapy in patients with NMIBC. The results indicated that the involved mechanism occurred via upregulation of PD-L1 by immune cytokines, which in turn suppressed the antitumor effectiveness of the immune system, thereby promoting tumor recurrence and progression.

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OK-432 Suppresses Proliferation and Metastasis by Tumor Associated Macrophages in Bladder Cancer

Cited by 14 publications

References 28 publications

Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model

Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model

Bladder cancer cells interact with vascular endothelial cells triggering EGFR signals to promote tumor progression

Effects of programmed death-ligand 1 expression on OK-432 immunotherapy following transurethral resection in non-muscle invasive bladder cancer

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