The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer
IntroductionBladder cancer (BLCA) is a highly malignant tumor of the urinary system, but the prognosis and survival rates have little improvement based on current therapeutic strategy. Immune checkpoint inhibitors (ICIs) therapy revolutionized the treatment of BLCA, but the clinical application of I...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1085476/full |
| _version_ | 1811159008869875712 |
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| author | Zihan Zhao Siyang Liu Rui Sun Wenjie Zhu Yulin Zhang Tianyao Liu Tianhang Li Ning Jiang Hongqian Guo Rong Yang |
| author_facet | Zihan Zhao Siyang Liu Rui Sun Wenjie Zhu Yulin Zhang Tianyao Liu Tianhang Li Ning Jiang Hongqian Guo Rong Yang |
| author_sort | Zihan Zhao |
| collection | DOAJ |
| description | IntroductionBladder cancer (BLCA) is a highly malignant tumor of the urinary system, but the prognosis and survival rates have little improvement based on current therapeutic strategy. Immune checkpoint inhibitors (ICIs) therapy revolutionized the treatment of BLCA, but the clinical application of ICIs is limited by low response rate. Oxaliplatin (OXP), a second line chemotherapy drug for BLCA, may reshape the tumor immune microenvironment (TIME) via recruiting immune cells. Here, we conducted the study of oxaliplatin combined with anti-PD-1 inhibitor in BLCA mice models.MethodsThe 6-8 weeks old female C57BL/6J mice were used to establish subcutaneous model of bladder tumor. After tumors developed, mice were given tail vein injections of PBS or oxaliplatin (2.5 mg/kg) and/or anti-PD-1 antibody (10 mg/kg). Tumor tissue samples and peripheral blood mononuclear cell (PBMC) were collected to systemically evaluate the efficiency and safety of combination OXP and anti-PD-1 inhibitor. The change of immune cells populations and the corresponding phenotypic diversity in TIME and PBMC were analysed by flow cytometry.ResultsTumor growth experiments clarified that the combination therapy was more efficient than medication alone. Flow cytometry analysis of tumor samples showed significant differences between untreated and treated mice. Oxaliplatin influences the TIME by increasing immune cells infiltration, including CD3+ T cells, CD4+ T cells, CD8+ T cells, dendritic cells (DC cells) and natural killer cells (NK cells). As for infiltrating cells, oxaliplatin upregulated the expression of CD134 and downregulated TIM-3 of CD4+ T cells, downregulated the PD-L1 expression of DC cells, which contributed to improve the anti-tumor effect and the treatment response of ICIs. Additionally, the evaluation of PBMC found that there were no significant changes in immune cell subsets and phenotypes, which validated the safety of the combination therapy. These results show the therapeutic potential for the combination of OXP and anti-PD-1 inhibitor in BLCA.ConclusionOXP could increase the infiltration of immune cells in TIME to promote the anti-tumor activity of anti-PD-1 inhibitor. The present research provided an appropriate rationale of combination chemotherapy and immunotherapy therapy for BLCA. |
| first_indexed | 2024-04-10T05:33:54Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T05:33:54Z |
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| spelling | doaj.art-cd3583cb4beb463db5abab27d7fda4be2023-03-07T04:49:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.10854761085476The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancerZihan Zhao0Siyang Liu1Rui Sun2Wenjie Zhu3Yulin Zhang4Tianyao Liu5Tianhang Li6Ning Jiang7Hongqian Guo8Rong Yang9Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, ChinaDepartment of Urology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, ChinaDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, ChinaDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, ChinaIntroductionBladder cancer (BLCA) is a highly malignant tumor of the urinary system, but the prognosis and survival rates have little improvement based on current therapeutic strategy. Immune checkpoint inhibitors (ICIs) therapy revolutionized the treatment of BLCA, but the clinical application of ICIs is limited by low response rate. Oxaliplatin (OXP), a second line chemotherapy drug for BLCA, may reshape the tumor immune microenvironment (TIME) via recruiting immune cells. Here, we conducted the study of oxaliplatin combined with anti-PD-1 inhibitor in BLCA mice models.MethodsThe 6-8 weeks old female C57BL/6J mice were used to establish subcutaneous model of bladder tumor. After tumors developed, mice were given tail vein injections of PBS or oxaliplatin (2.5 mg/kg) and/or anti-PD-1 antibody (10 mg/kg). Tumor tissue samples and peripheral blood mononuclear cell (PBMC) were collected to systemically evaluate the efficiency and safety of combination OXP and anti-PD-1 inhibitor. The change of immune cells populations and the corresponding phenotypic diversity in TIME and PBMC were analysed by flow cytometry.ResultsTumor growth experiments clarified that the combination therapy was more efficient than medication alone. Flow cytometry analysis of tumor samples showed significant differences between untreated and treated mice. Oxaliplatin influences the TIME by increasing immune cells infiltration, including CD3+ T cells, CD4+ T cells, CD8+ T cells, dendritic cells (DC cells) and natural killer cells (NK cells). As for infiltrating cells, oxaliplatin upregulated the expression of CD134 and downregulated TIM-3 of CD4+ T cells, downregulated the PD-L1 expression of DC cells, which contributed to improve the anti-tumor effect and the treatment response of ICIs. Additionally, the evaluation of PBMC found that there were no significant changes in immune cell subsets and phenotypes, which validated the safety of the combination therapy. These results show the therapeutic potential for the combination of OXP and anti-PD-1 inhibitor in BLCA.ConclusionOXP could increase the infiltration of immune cells in TIME to promote the anti-tumor activity of anti-PD-1 inhibitor. The present research provided an appropriate rationale of combination chemotherapy and immunotherapy therapy for BLCA.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1085476/fullbladder canceroxaliplatinimmunotherapycombination therapyimmune checkpoint inhibitorstumor immune microenvironment |
| spellingShingle | Zihan Zhao Siyang Liu Rui Sun Wenjie Zhu Yulin Zhang Tianyao Liu Tianhang Li Ning Jiang Hongqian Guo Rong Yang The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer Frontiers in Immunology bladder cancer oxaliplatin immunotherapy combination therapy immune checkpoint inhibitors tumor immune microenvironment |
| title | The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer |
| title_full | The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer |
| title_fullStr | The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer |
| title_full_unstemmed | The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer |
| title_short | The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer |
| title_sort | combination of oxaliplatin and anti pd 1 inhibitor promotes immune cells infiltration and enhances anti tumor effect of pd 1 blockade in bladder cancer |
| topic | bladder cancer oxaliplatin immunotherapy combination therapy immune checkpoint inhibitors tumor immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1085476/full |
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