Apatinib potentiates the therapeutic effect of anti‐PD‐1 in locally advanced head and neck cancers

Objectives Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood. Patients and Methods We investigate the impact of VEGFR2 inhibition on tumor‐infiltrating immune cells in vivo and th...

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Veröffentlicht in:Oral diseases 2024-07, Vol.30 (5), p.2940-2951
Hauptverfasser: Liu, Shuli, Zhang, Lin, Ye, Weimin, Zhou, Rong, Gu, Ziyue, Shi, Chaoji, Xu, Shengming, Li, Jiang, Zhang, Zhiyuan, Han, Yong
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container_end_page 2951
container_issue 5
container_start_page 2940
container_title Oral diseases
container_volume 30
creator Liu, Shuli
Zhang, Lin
Ye, Weimin
Zhou, Rong
Gu, Ziyue
Shi, Chaoji
Xu, Shengming
Li, Jiang
Zhang, Zhiyuan
Han, Yong
description Objectives Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood. Patients and Methods We investigate the impact of VEGFR2 inhibition on tumor‐infiltrating immune cells in vivo and the activity of the combination of apatinib and anti‐PD‐1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery. Results We found that apatinib increased the infiltration of CD8+T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+PD1+T cells were significantly increased in apatinib‐treated tumors. The combined treatment of apatinib and anti‐PD‐1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment. Conclusion Our study demonstrated that apatinib therapy synergized with an anti–PD‐1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC.
doi_str_mv 10.1111/odi.14768
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Patients and Methods We investigate the impact of VEGFR2 inhibition on tumor‐infiltrating immune cells in vivo and the activity of the combination of apatinib and anti‐PD‐1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery. Results We found that apatinib increased the infiltration of CD8+T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+PD1+T cells were significantly increased in apatinib‐treated tumors. The combined treatment of apatinib and anti‐PD‐1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment. Conclusion Our study demonstrated that apatinib therapy synergized with an anti–PD‐1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC.</description><identifier>ISSN: 1354-523X</identifier><identifier>ISSN: 1601-0825</identifier><identifier>EISSN: 1601-0825</identifier><identifier>DOI: 10.1111/odi.14768</identifier><identifier>PMID: 37846172</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Angiogenesis Inhibitors - pharmacology ; Angiogenesis Inhibitors - therapeutic use ; Animal models ; Animals ; Antibodies, Monoclonal, Humanized - pharmacology ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; apatinib ; Cancer ; CD8 antigen ; CD8-Positive T-Lymphocytes - drug effects ; Cervical carcinoma ; Clinical trials ; Drug Synergism ; Female ; Head &amp; neck cancer ; Head and neck carcinoma ; Head and Neck Neoplasms - drug therapy ; head and neck squamous cell carcinoma ; Humans ; Immune checkpoint inhibitors ; Immune Checkpoint Inhibitors - pharmacology ; Immune Checkpoint Inhibitors - therapeutic use ; Immunotherapy ; Lymph nodes ; Lymphatic system ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - drug effects ; Lymphocytes, Tumor-Infiltrating - immunology ; Male ; Metastases ; Mice ; neoadjuvant immunotherapy ; Neoadjuvant Therapy ; Patients ; PD-1 protein ; PD‐1 blockade ; Programmed Cell Death 1 Receptor - antagonists &amp; inhibitors ; Pyridines - pharmacology ; Pyridines - therapeutic use ; Squamous cell carcinoma ; Squamous Cell Carcinoma of Head and Neck - drug therapy ; Synergism ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; Tongue ; Tongue Neoplasms - drug therapy ; Tongue Neoplasms - pathology ; Vascular Endothelial Growth Factor Receptor-2 - antagonists &amp; inhibitors</subject><ispartof>Oral diseases, 2024-07, Vol.30 (5), p.2940-2951</ispartof><rights>2023 Wiley Periodicals LLC.</rights><rights>2024 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3538-890a567edcaa94957f4e9a0d5a632fe379ffd7d946b168860dea0a1c42eb9c4c3</citedby><cites>FETCH-LOGICAL-c3538-890a567edcaa94957f4e9a0d5a632fe379ffd7d946b168860dea0a1c42eb9c4c3</cites><orcidid>0000-0002-9456-5656 ; 0000-0003-0327-2100 ; 0000-0003-3845-7420 ; 0000-0002-8856-5772</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fodi.14768$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fodi.14768$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37846172$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Shuli</creatorcontrib><creatorcontrib>Zhang, Lin</creatorcontrib><creatorcontrib>Ye, Weimin</creatorcontrib><creatorcontrib>Zhou, Rong</creatorcontrib><creatorcontrib>Gu, Ziyue</creatorcontrib><creatorcontrib>Shi, Chaoji</creatorcontrib><creatorcontrib>Xu, Shengming</creatorcontrib><creatorcontrib>Li, Jiang</creatorcontrib><creatorcontrib>Zhang, Zhiyuan</creatorcontrib><creatorcontrib>Han, Yong</creatorcontrib><title>Apatinib potentiates the therapeutic effect of anti‐PD‐1 in locally advanced head and neck cancers</title><title>Oral diseases</title><addtitle>Oral Dis</addtitle><description>Objectives Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood. Patients and Methods We investigate the impact of VEGFR2 inhibition on tumor‐infiltrating immune cells in vivo and the activity of the combination of apatinib and anti‐PD‐1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery. Results We found that apatinib increased the infiltration of CD8+T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+PD1+T cells were significantly increased in apatinib‐treated tumors. The combined treatment of apatinib and anti‐PD‐1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment. Conclusion Our study demonstrated that apatinib therapy synergized with an anti–PD‐1 antibody in preclinical cancer models and in patient with advanced HNSCC. 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inhibitors</subject><subject>Pyridines - pharmacology</subject><subject>Pyridines - therapeutic use</subject><subject>Squamous cell carcinoma</subject><subject>Squamous Cell Carcinoma of Head and Neck - drug therapy</subject><subject>Synergism</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Tongue</subject><subject>Tongue Neoplasms - drug therapy</subject><subject>Tongue Neoplasms - pathology</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - antagonists &amp; inhibitors</subject><issn>1354-523X</issn><issn>1601-0825</issn><issn>1601-0825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10M1KHTEYBuBQKmqti95ACXRjF6PJJJOfpfhXQdBFC92F7yRfMHbOzHQyo5ydl-A19krM6bEuCgaSL4SHl_AS8omzQ17WUR_SIZdamXdklyvGK2bq5n25i0ZWTS1-7pAPOd8xxrUV9TbZEdpIxXW9S-LxAFPq0oIO_YTdlGDCTKdbXO8RBpyn5CnGiH6ifaRQyJ_Hp5vTcnCaOtr2Htp2RSHcQ-cx0FuEUFigHfpf1K8fx_yRbEVoM-6_zD3y4_zs-8m36ur64vLk-KryohGmMpZBozQGD2ClbXSUaIGFBpSoIwptYww6WKkWXBmjWEBgwL2scWG99GKPHGxyh7H_PWOe3DJlj20LHfZzdrXRprbCSl7ol__oXT-PXfmdE6U_rTTnoqivG-XHPucRoxvGtIRx5Thz6_JdKd_9Lb_Yzy-J82KJ4VX-a7uAow14SC2u3k5y16eXm8hnBiKPvg</recordid><startdate>202407</startdate><enddate>202407</enddate><creator>Liu, Shuli</creator><creator>Zhang, Lin</creator><creator>Ye, Weimin</creator><creator>Zhou, Rong</creator><creator>Gu, Ziyue</creator><creator>Shi, Chaoji</creator><creator>Xu, Shengming</creator><creator>Li, Jiang</creator><creator>Zhang, Zhiyuan</creator><creator>Han, Yong</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9456-5656</orcidid><orcidid>https://orcid.org/0000-0003-0327-2100</orcidid><orcidid>https://orcid.org/0000-0003-3845-7420</orcidid><orcidid>https://orcid.org/0000-0002-8856-5772</orcidid></search><sort><creationdate>202407</creationdate><title>Apatinib potentiates the therapeutic effect of anti‐PD‐1 in locally advanced head and neck cancers</title><author>Liu, Shuli ; Zhang, Lin ; Ye, Weimin ; Zhou, Rong ; Gu, Ziyue ; Shi, Chaoji ; Xu, Shengming ; Li, Jiang ; Zhang, Zhiyuan ; Han, Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3538-890a567edcaa94957f4e9a0d5a632fe379ffd7d946b168860dea0a1c42eb9c4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Angiogenesis Inhibitors - therapeutic use</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antibodies, Monoclonal, Humanized - pharmacology</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>apatinib</topic><topic>Cancer</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - drug effects</topic><topic>Cervical carcinoma</topic><topic>Clinical trials</topic><topic>Drug Synergism</topic><topic>Female</topic><topic>Head &amp; neck cancer</topic><topic>Head and neck carcinoma</topic><topic>Head and Neck Neoplasms - drug therapy</topic><topic>head and neck squamous cell carcinoma</topic><topic>Humans</topic><topic>Immune checkpoint inhibitors</topic><topic>Immune Checkpoint Inhibitors - pharmacology</topic><topic>Immune Checkpoint Inhibitors - therapeutic use</topic><topic>Immunotherapy</topic><topic>Lymph nodes</topic><topic>Lymphatic system</topic><topic>Lymphocytes T</topic><topic>Lymphocytes, Tumor-Infiltrating - drug effects</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Male</topic><topic>Metastases</topic><topic>Mice</topic><topic>neoadjuvant immunotherapy</topic><topic>Neoadjuvant Therapy</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>PD‐1 blockade</topic><topic>Programmed Cell Death 1 Receptor - antagonists &amp; inhibitors</topic><topic>Pyridines - pharmacology</topic><topic>Pyridines - therapeutic use</topic><topic>Squamous cell carcinoma</topic><topic>Squamous Cell Carcinoma of Head and Neck - drug therapy</topic><topic>Synergism</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Tongue</topic><topic>Tongue Neoplasms - drug therapy</topic><topic>Tongue Neoplasms - pathology</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - antagonists &amp; inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Shuli</creatorcontrib><creatorcontrib>Zhang, Lin</creatorcontrib><creatorcontrib>Ye, Weimin</creatorcontrib><creatorcontrib>Zhou, Rong</creatorcontrib><creatorcontrib>Gu, Ziyue</creatorcontrib><creatorcontrib>Shi, Chaoji</creatorcontrib><creatorcontrib>Xu, Shengming</creatorcontrib><creatorcontrib>Li, Jiang</creatorcontrib><creatorcontrib>Zhang, Zhiyuan</creatorcontrib><creatorcontrib>Han, Yong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Oral diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Shuli</au><au>Zhang, Lin</au><au>Ye, Weimin</au><au>Zhou, Rong</au><au>Gu, Ziyue</au><au>Shi, Chaoji</au><au>Xu, Shengming</au><au>Li, Jiang</au><au>Zhang, Zhiyuan</au><au>Han, Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apatinib potentiates the therapeutic effect of anti‐PD‐1 in locally advanced head and neck cancers</atitle><jtitle>Oral diseases</jtitle><addtitle>Oral Dis</addtitle><date>2024-07</date><risdate>2024</risdate><volume>30</volume><issue>5</issue><spage>2940</spage><epage>2951</epage><pages>2940-2951</pages><issn>1354-523X</issn><issn>1601-0825</issn><eissn>1601-0825</eissn><abstract>Objectives Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood. Patients and Methods We investigate the impact of VEGFR2 inhibition on tumor‐infiltrating immune cells in vivo and the activity of the combination of apatinib and anti‐PD‐1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery. Results We found that apatinib increased the infiltration of CD8+T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+PD1+T cells were significantly increased in apatinib‐treated tumors. The combined treatment of apatinib and anti‐PD‐1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment. Conclusion Our study demonstrated that apatinib therapy synergized with an anti–PD‐1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37846172</pmid><doi>10.1111/odi.14768</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9456-5656</orcidid><orcidid>https://orcid.org/0000-0003-0327-2100</orcidid><orcidid>https://orcid.org/0000-0003-3845-7420</orcidid><orcidid>https://orcid.org/0000-0002-8856-5772</orcidid></addata></record>
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subjects Angiogenesis Inhibitors - pharmacology
Angiogenesis Inhibitors - therapeutic use
Animal models
Animals
Antibodies, Monoclonal, Humanized - pharmacology
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
apatinib
Cancer
CD8 antigen
CD8-Positive T-Lymphocytes - drug effects
Cervical carcinoma
Clinical trials
Drug Synergism
Female
Head & neck cancer
Head and neck carcinoma
Head and Neck Neoplasms - drug therapy
head and neck squamous cell carcinoma
Humans
Immune checkpoint inhibitors
Immune Checkpoint Inhibitors - pharmacology
Immune Checkpoint Inhibitors - therapeutic use
Immunotherapy
Lymph nodes
Lymphatic system
Lymphocytes T
Lymphocytes, Tumor-Infiltrating - drug effects
Lymphocytes, Tumor-Infiltrating - immunology
Male
Metastases
Mice
neoadjuvant immunotherapy
Neoadjuvant Therapy
Patients
PD-1 protein
PD‐1 blockade
Programmed Cell Death 1 Receptor - antagonists & inhibitors
Pyridines - pharmacology
Pyridines - therapeutic use
Squamous cell carcinoma
Squamous Cell Carcinoma of Head and Neck - drug therapy
Synergism
T-Lymphocytes, Regulatory - drug effects
T-Lymphocytes, Regulatory - immunology
Tongue
Tongue Neoplasms - drug therapy
Tongue Neoplasms - pathology
Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors
title Apatinib potentiates the therapeutic effect of anti‐PD‐1 in locally advanced head and neck cancers
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