Apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression
•Apatinib treatment increased PD-L1 expression in various colon cancer cells.•Apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells.•The combination of apatinib with anti-PD-1 significantly inhibited colon cancer growth in mice. Increasing studies confirm that anti-angioge...
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| Veröffentlicht in: | International immunopharmacology 2020-11, Vol.88, p.106858-106858, Article 106858 |
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| container_title | International immunopharmacology |
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| creator | Cai, Xiaomin Wei, Bin Li, Lele Chen, Xiaofeng Liu, Wen Cui, Jian Lin, Yumeng Sun, Yang Xu, Qiang Guo, Wenjie Gu, Yanhong |
| description | •Apatinib treatment increased PD-L1 expression in various colon cancer cells.•Apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells.•The combination of apatinib with anti-PD-1 significantly inhibited colon cancer growth in mice.
Increasing studies confirm that anti-angiogenesis can increase the effectiveness of immunotherapy. In this study, we found that an angiogenesis inhibitor apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression. Apatinib treatment upregulated PD-L1 expression in various colon cancer cells both at the mRNA and protein levels. Further, apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells in the co-culture system, which was reversed by the anti-PD-1 antibody. Based on this, the combination of apatinib with anti-PD-1 on colon cancer growth in mice was examined. The combination treatment showed more significant inhibition on the growth of transplanted tumors in mice than single-drug treatment. Overall, our study here showed the enhancement of anti-PD-1 antitumor efficacy in a syngeneic mouse model (CT-26 cells in Balb/c) by the angiogenesis inhibitor apatinib via upregulating PD-L1 expression as well as angiogenesis inhibition, which may provide a rationale for the combination of apatinib and anti-PD-1 antibody for colorectal cancer treatment in the clinic. |
| doi_str_mv | 10.1016/j.intimp.2020.106858 |
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Increasing studies confirm that anti-angiogenesis can increase the effectiveness of immunotherapy. In this study, we found that an angiogenesis inhibitor apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression. Apatinib treatment upregulated PD-L1 expression in various colon cancer cells both at the mRNA and protein levels. Further, apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells in the co-culture system, which was reversed by the anti-PD-1 antibody. Based on this, the combination of apatinib with anti-PD-1 on colon cancer growth in mice was examined. The combination treatment showed more significant inhibition on the growth of transplanted tumors in mice than single-drug treatment. Overall, our study here showed the enhancement of anti-PD-1 antitumor efficacy in a syngeneic mouse model (CT-26 cells in Balb/c) by the angiogenesis inhibitor apatinib via upregulating PD-L1 expression as well as angiogenesis inhibition, which may provide a rationale for the combination of apatinib and anti-PD-1 antibody for colorectal cancer treatment in the clinic.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2020.106858</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Angiogenesis ; Angiogenesis inhibitors ; Antibodies ; Anticancer properties ; Antitumor activity ; Apatinib ; Cell activation ; Cell culture ; Colon ; Colon cancer ; Colorectal cancer ; Colorectal carcinoma ; Immunotherapy ; Inhibitors ; Lymphocytes ; Lymphocytes T ; mRNA ; PD-1 protein ; PD-L1 ; PD-L1 protein ; T cell ; Tumors ; γ-Interferon</subject><ispartof>International immunopharmacology, 2020-11, Vol.88, p.106858-106858, Article 106858</ispartof><rights>2020 The Authors</rights><rights>Copyright Elsevier BV Nov 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-3adcbe1f0646eff81f385a03f7ea1f039f661cf758900a3fa1c0ed6a873e5c6d3</citedby><cites>FETCH-LOGICAL-c479t-3adcbe1f0646eff81f385a03f7ea1f039f661cf758900a3fa1c0ed6a873e5c6d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2020.106858$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids></links><search><creatorcontrib>Cai, Xiaomin</creatorcontrib><creatorcontrib>Wei, Bin</creatorcontrib><creatorcontrib>Li, Lele</creatorcontrib><creatorcontrib>Chen, Xiaofeng</creatorcontrib><creatorcontrib>Liu, Wen</creatorcontrib><creatorcontrib>Cui, Jian</creatorcontrib><creatorcontrib>Lin, Yumeng</creatorcontrib><creatorcontrib>Sun, Yang</creatorcontrib><creatorcontrib>Xu, Qiang</creatorcontrib><creatorcontrib>Guo, Wenjie</creatorcontrib><creatorcontrib>Gu, Yanhong</creatorcontrib><title>Apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression</title><title>International immunopharmacology</title><description>•Apatinib treatment increased PD-L1 expression in various colon cancer cells.•Apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells.•The combination of apatinib with anti-PD-1 significantly inhibited colon cancer growth in mice.
Increasing studies confirm that anti-angiogenesis can increase the effectiveness of immunotherapy. In this study, we found that an angiogenesis inhibitor apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression. Apatinib treatment upregulated PD-L1 expression in various colon cancer cells both at the mRNA and protein levels. Further, apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells in the co-culture system, which was reversed by the anti-PD-1 antibody. Based on this, the combination of apatinib with anti-PD-1 on colon cancer growth in mice was examined. The combination treatment showed more significant inhibition on the growth of transplanted tumors in mice than single-drug treatment. Overall, our study here showed the enhancement of anti-PD-1 antitumor efficacy in a syngeneic mouse model (CT-26 cells in Balb/c) by the angiogenesis inhibitor apatinib via upregulating PD-L1 expression as well as angiogenesis inhibition, which may provide a rationale for the combination of apatinib and anti-PD-1 antibody for colorectal cancer treatment in the clinic.</description><subject>Angiogenesis</subject><subject>Angiogenesis inhibitors</subject><subject>Antibodies</subject><subject>Anticancer properties</subject><subject>Antitumor activity</subject><subject>Apatinib</subject><subject>Cell activation</subject><subject>Cell culture</subject><subject>Colon</subject><subject>Colon cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Immunotherapy</subject><subject>Inhibitors</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>mRNA</subject><subject>PD-1 protein</subject><subject>PD-L1</subject><subject>PD-L1 protein</subject><subject>T cell</subject><subject>Tumors</subject><subject>γ-Interferon</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kDtPwzAUhSMEEqXwDxgssbCk2HnYzoJUladUCQaYGCzXuaaOEjvYaUX_PY7CxMB0r46-c3TvSZJLghcEE3rTLIwdTNcvMpyNEuUlP0pmhDOeEobL47iXlKUlo9VpchZCg3HUCzJLPpa9HIw1GwR2K62CGsmYlb7epQQNW_CyPyDtPFKudRapEfHIWNQZBWhvJOq961yM-ETRsyYIvnsPIRhnz5MTLdsAF79znrw_3L-tntL1y-PzarlOVcGqIc1lrTZANKYFBa050TkvJc41AxnVvNKUEqVZySuMZa4lURhqKjnLoVS0zufJ9ZQbT_naQRhEZ4KCtpUW3C6IrMiLgmUlzyJ69Qdt3M7beF2kGOdZVmAcqWKilHcheNCi96aT_iAIFmPjohFT42JsXEyNR9vtZIP47N6AF0EZGDs1HtQgamf-D_gBqHWK1A</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Cai, Xiaomin</creator><creator>Wei, Bin</creator><creator>Li, Lele</creator><creator>Chen, Xiaofeng</creator><creator>Liu, Wen</creator><creator>Cui, Jian</creator><creator>Lin, Yumeng</creator><creator>Sun, Yang</creator><creator>Xu, Qiang</creator><creator>Guo, Wenjie</creator><creator>Gu, Yanhong</creator><general>Elsevier B.V</general><general>Elsevier BV</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>202011</creationdate><title>Apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression</title><author>Cai, Xiaomin ; Wei, Bin ; Li, Lele ; Chen, Xiaofeng ; Liu, Wen ; Cui, Jian ; Lin, Yumeng ; Sun, Yang ; Xu, Qiang ; Guo, Wenjie ; Gu, Yanhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-3adcbe1f0646eff81f385a03f7ea1f039f661cf758900a3fa1c0ed6a873e5c6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Angiogenesis</topic><topic>Angiogenesis inhibitors</topic><topic>Antibodies</topic><topic>Anticancer properties</topic><topic>Antitumor activity</topic><topic>Apatinib</topic><topic>Cell activation</topic><topic>Cell culture</topic><topic>Colon</topic><topic>Colon cancer</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Immunotherapy</topic><topic>Inhibitors</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>mRNA</topic><topic>PD-1 protein</topic><topic>PD-L1</topic><topic>PD-L1 protein</topic><topic>T cell</topic><topic>Tumors</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cai, Xiaomin</creatorcontrib><creatorcontrib>Wei, Bin</creatorcontrib><creatorcontrib>Li, Lele</creatorcontrib><creatorcontrib>Chen, Xiaofeng</creatorcontrib><creatorcontrib>Liu, Wen</creatorcontrib><creatorcontrib>Cui, Jian</creatorcontrib><creatorcontrib>Lin, Yumeng</creatorcontrib><creatorcontrib>Sun, Yang</creatorcontrib><creatorcontrib>Xu, Qiang</creatorcontrib><creatorcontrib>Guo, Wenjie</creatorcontrib><creatorcontrib>Gu, Yanhong</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Xiaomin</au><au>Wei, Bin</au><au>Li, Lele</au><au>Chen, Xiaofeng</au><au>Liu, Wen</au><au>Cui, Jian</au><au>Lin, Yumeng</au><au>Sun, Yang</au><au>Xu, Qiang</au><au>Guo, Wenjie</au><au>Gu, Yanhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression</atitle><jtitle>International immunopharmacology</jtitle><date>2020-11</date><risdate>2020</risdate><volume>88</volume><spage>106858</spage><epage>106858</epage><pages>106858-106858</pages><artnum>106858</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>•Apatinib treatment increased PD-L1 expression in various colon cancer cells.•Apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells.•The combination of apatinib with anti-PD-1 significantly inhibited colon cancer growth in mice.
Increasing studies confirm that anti-angiogenesis can increase the effectiveness of immunotherapy. In this study, we found that an angiogenesis inhibitor apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression. Apatinib treatment upregulated PD-L1 expression in various colon cancer cells both at the mRNA and protein levels. Further, apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells in the co-culture system, which was reversed by the anti-PD-1 antibody. Based on this, the combination of apatinib with anti-PD-1 on colon cancer growth in mice was examined. The combination treatment showed more significant inhibition on the growth of transplanted tumors in mice than single-drug treatment. Overall, our study here showed the enhancement of anti-PD-1 antitumor efficacy in a syngeneic mouse model (CT-26 cells in Balb/c) by the angiogenesis inhibitor apatinib via upregulating PD-L1 expression as well as angiogenesis inhibition, which may provide a rationale for the combination of apatinib and anti-PD-1 antibody for colorectal cancer treatment in the clinic.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><doi>10.1016/j.intimp.2020.106858</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Angiogenesis inhibitors Antibodies Anticancer properties Antitumor activity Apatinib Cell activation Cell culture Colon Colon cancer Colorectal cancer Colorectal carcinoma Immunotherapy Inhibitors Lymphocytes Lymphocytes T mRNA PD-1 protein PD-L1 PD-L1 protein T cell Tumors γ-Interferon |
| title | Apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression |
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