Sequential treatment of anti-PD-L1 therapy prior to anti-VEGFR2 therapy contributes to more significant clinical benefits in non-small cell lung cancer
Objective: Anti-angiogenic therapy and immune checkpoint blockade therapy are currently important treatments for non-small cell lung cancer. However, the combined use of the two therapies is controversial, and few studies have investigated the effects of different time sequences of the two therapies...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558624001180 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846119481965805568 |
|---|---|
| author | Qiao-xin Lin Wen-wen Song Wen-xia Xie Yi-ting Deng Yan-na Gong Yi-ru Liu Yi Tian Wen-ya Zhao Ling Tian Dian-na Gu |
| author_facet | Qiao-xin Lin Wen-wen Song Wen-xia Xie Yi-ting Deng Yan-na Gong Yi-ru Liu Yi Tian Wen-ya Zhao Ling Tian Dian-na Gu |
| author_sort | Qiao-xin Lin |
| collection | DOAJ |
| description | Objective: Anti-angiogenic therapy and immune checkpoint blockade therapy are currently important treatments for non-small cell lung cancer. However, the combined use of the two therapies is controversial, and few studies have investigated the effects of different time sequences of the two therapies on treatment outcomes. Methods: The tumor-bearing mouse model was established and the mice were divided into four groups, including AA-ICB sequence group, ICB-AA sequence group, synchronization group and the control group. Immunohistochemistry was used to assess tumor microvessels and PD-L1 expression. Selected immune cell populations were evaluated using flow cytometry. Meta-analysis and clinical information were used to elucidate the clinical effects of administration sequence. Results: We found that anti-PD-L1 treatment followed by anti-VEGFR2 therapy exerts the best inhibitory effect on tumor growth. Different sequences of anti-angiogenic therapy and immune checkpoint blockade therapy resulted in different proportions of tumor microvessels and immune cell populations in the tumor microenvironment. We further revealed that the administration of anti-PD-L1 before anti-VEGFR brought more normalized tumor blood vessels and CD8+T cell infiltration and reduced immunosuppressive cells in the tumor microenvironment. Subsequent re-transplantation experiments confirmed the long-term benefits of this treatment strategy. The meta-analysis reinforced that immunotherapy prior to anti-angiogenic therapy or combination therapy have better therapeutic effects in advanced non-small cell lung cancer. Conclusion: Our study demonstrated that the therapeutic effect of anti-angiogenic treatment after immune checkpoint therapy was superior to that of concurrent therapy, whereas anti-angiogenic therapy followed by immunotherapy did not bring more significant clinical benefits than independent monotherapy. |
| format | Article |
| id | doaj-art-74e44febb7d7493788a3bb40b1c0df5a |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-74e44febb7d7493788a3bb40b1c0df5a2024-12-17T04:59:00ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-01-0159101077Sequential treatment of anti-PD-L1 therapy prior to anti-VEGFR2 therapy contributes to more significant clinical benefits in non-small cell lung cancerQiao-xin Lin0Wen-wen Song1Wen-xia Xie2Yi-ting Deng3Yan-na Gong4Yi-ru Liu5Yi Tian6Wen-ya Zhao7Ling Tian8Dian-na Gu9Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authors.Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Corresponding authors.Objective: Anti-angiogenic therapy and immune checkpoint blockade therapy are currently important treatments for non-small cell lung cancer. However, the combined use of the two therapies is controversial, and few studies have investigated the effects of different time sequences of the two therapies on treatment outcomes. Methods: The tumor-bearing mouse model was established and the mice were divided into four groups, including AA-ICB sequence group, ICB-AA sequence group, synchronization group and the control group. Immunohistochemistry was used to assess tumor microvessels and PD-L1 expression. Selected immune cell populations were evaluated using flow cytometry. Meta-analysis and clinical information were used to elucidate the clinical effects of administration sequence. Results: We found that anti-PD-L1 treatment followed by anti-VEGFR2 therapy exerts the best inhibitory effect on tumor growth. Different sequences of anti-angiogenic therapy and immune checkpoint blockade therapy resulted in different proportions of tumor microvessels and immune cell populations in the tumor microenvironment. We further revealed that the administration of anti-PD-L1 before anti-VEGFR brought more normalized tumor blood vessels and CD8+T cell infiltration and reduced immunosuppressive cells in the tumor microenvironment. Subsequent re-transplantation experiments confirmed the long-term benefits of this treatment strategy. The meta-analysis reinforced that immunotherapy prior to anti-angiogenic therapy or combination therapy have better therapeutic effects in advanced non-small cell lung cancer. Conclusion: Our study demonstrated that the therapeutic effect of anti-angiogenic treatment after immune checkpoint therapy was superior to that of concurrent therapy, whereas anti-angiogenic therapy followed by immunotherapy did not bring more significant clinical benefits than independent monotherapy.http://www.sciencedirect.com/science/article/pii/S1476558624001180Immune checkpoint blockade therapyAnti-angiogenic therapySequential therapyNon-small cell lung cancerTumor microvesselTumor immune microenvironment |
| spellingShingle | Qiao-xin Lin Wen-wen Song Wen-xia Xie Yi-ting Deng Yan-na Gong Yi-ru Liu Yi Tian Wen-ya Zhao Ling Tian Dian-na Gu Sequential treatment of anti-PD-L1 therapy prior to anti-VEGFR2 therapy contributes to more significant clinical benefits in non-small cell lung cancer Neoplasia: An International Journal for Oncology Research Immune checkpoint blockade therapy Anti-angiogenic therapy Sequential therapy Non-small cell lung cancer Tumor microvessel Tumor immune microenvironment |
| title | Sequential treatment of anti-PD-L1 therapy prior to anti-VEGFR2 therapy contributes to more significant clinical benefits in non-small cell lung cancer |
| title_full | Sequential treatment of anti-PD-L1 therapy prior to anti-VEGFR2 therapy contributes to more significant clinical benefits in non-small cell lung cancer |
| title_fullStr | Sequential treatment of anti-PD-L1 therapy prior to anti-VEGFR2 therapy contributes to more significant clinical benefits in non-small cell lung cancer |
| title_full_unstemmed | Sequential treatment of anti-PD-L1 therapy prior to anti-VEGFR2 therapy contributes to more significant clinical benefits in non-small cell lung cancer |
| title_short | Sequential treatment of anti-PD-L1 therapy prior to anti-VEGFR2 therapy contributes to more significant clinical benefits in non-small cell lung cancer |
| title_sort | sequential treatment of anti pd l1 therapy prior to anti vegfr2 therapy contributes to more significant clinical benefits in non small cell lung cancer |
| topic | Immune checkpoint blockade therapy Anti-angiogenic therapy Sequential therapy Non-small cell lung cancer Tumor microvessel Tumor immune microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S1476558624001180 |
| work_keys_str_mv | AT qiaoxinlin sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer AT wenwensong sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer AT wenxiaxie sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer AT yitingdeng sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer AT yannagong sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer AT yiruliu sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer AT yitian sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer AT wenyazhao sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer AT lingtian sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer AT diannagu sequentialtreatmentofantipdl1therapypriortoantivegfr2therapycontributestomoresignificantclinicalbenefitsinnonsmallcelllungcancer |