Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer
Background CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. Methods The expression of CD47 in clini...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy : CII Immunotherapy : CII, 2024-03, Vol.73 (4), p.75, Article 75 |
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| creator | Zhang, Kaiqi Xu, Yuan Chang, Xusheng Xu, Caili Xue, Wenjing Ding, Dan Nie, Mingming Cai, Hui Xu, Jun Zhan, Lu Han, Jiangbo Cai, Tiancai Ju, Dianwen Feng, Li Zhang, Xuyao Yin, Kai |
| description | Background
CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear.
Methods
The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry.
Results
In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents.
Conclusions
Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy. |
| doi_str_mv | 10.1007/s00262-024-03667-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10965671</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2986647327</sourcerecordid><originalsourceid>FETCH-LOGICAL-c426t-adde45546a16a9afb81bf1640a440349271357bd17364a05f4ac4713ed0c9b733</originalsourceid><addsrcrecordid>eNp9kUtP3TAQha2qVaG3_QNdVJa6YRMYP2LHK4RueUlIbNpuLcdxUqNc-2I7SP33Nb2UAgtWtuZ8c2ZGB6HPBA4JgDzKAFTQBihvgAkhG_UG7RPOaqlrydsn_z30IecbAE5Bqfdoj3UtowS6fXS9jk0xaXLFhwmvv3GJTRjwz9PzM-xmb31xA97G4kKpQvFNWTYxYTeOzpaMfcCTySV5i60J1qWP6N1o5uw-Pbwr9OPs9Pv6orm6Pr9cn1w1llNRGjMMjrctF4YIo8zYd6QfieBgOAfGFZWEtbIfiGSCG2hHbiyvNTeAVb1kbIWOd77bpd-4wdb9kpn1NvmNSb91NF4_V4L_pad4pwko0YpqtUIHDw4p3i4uF73x2bp5NsHFJWsGdRFOoBUV_foCvYlLCvU-TVUnBJeMykrRHWVTzDm58XEbAvo-ML0LTNfA9N_AtKpNX57e8djyL6EKsB2QqxQml_7PfsX2D-qen1o</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2986647327</pqid></control><display><type>article</type><title>Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer</title><source>MEDLINE</source><source>Springer Nature OA Free Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>SpringerLink Journals - AutoHoldings</source><creator>Zhang, Kaiqi ; Xu, Yuan ; Chang, Xusheng ; Xu, Caili ; Xue, Wenjing ; Ding, Dan ; Nie, Mingming ; Cai, Hui ; Xu, Jun ; Zhan, Lu ; Han, Jiangbo ; Cai, Tiancai ; Ju, Dianwen ; Feng, Li ; Zhang, Xuyao ; Yin, Kai</creator><creatorcontrib>Zhang, Kaiqi ; Xu, Yuan ; Chang, Xusheng ; Xu, Caili ; Xue, Wenjing ; Ding, Dan ; Nie, Mingming ; Cai, Hui ; Xu, Jun ; Zhan, Lu ; Han, Jiangbo ; Cai, Tiancai ; Ju, Dianwen ; Feng, Li ; Zhang, Xuyao ; Yin, Kai</creatorcontrib><description>Background
CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear.
Methods
The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry.
Results
In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents.
Conclusions
Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.</description><identifier>ISSN: 1432-0851</identifier><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-024-03667-9</identifier><identifier>PMID: 38532108</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Angiogenesis ; Animals ; Cancer Research ; CD47 Antigen ; Disease Models, Animal ; Flow cytometry ; Fusion protein ; Gastric cancer ; Humans ; Immune checkpoint ; Immunohistochemistry ; Immunology ; Immunotherapy ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - metabolism ; Macrophages ; Malignancy ; Medical prognosis ; Medicine ; Medicine & Public Health ; Neoplasm Recurrence, Local ; Neoplasms ; Oncology ; Patients ; Peripheral blood mononuclear cells ; Phagocytosis ; Stomach Neoplasms ; Therapeutic targets ; Tumors ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A ; Xenografts</subject><ispartof>Cancer Immunology, Immunotherapy : CII, 2024-03, Vol.73 (4), p.75, Article 75</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c426t-adde45546a16a9afb81bf1640a440349271357bd17364a05f4ac4713ed0c9b733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965671/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965671/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,41120,41488,42189,42557,51319,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38532108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Kaiqi</creatorcontrib><creatorcontrib>Xu, Yuan</creatorcontrib><creatorcontrib>Chang, Xusheng</creatorcontrib><creatorcontrib>Xu, Caili</creatorcontrib><creatorcontrib>Xue, Wenjing</creatorcontrib><creatorcontrib>Ding, Dan</creatorcontrib><creatorcontrib>Nie, Mingming</creatorcontrib><creatorcontrib>Cai, Hui</creatorcontrib><creatorcontrib>Xu, Jun</creatorcontrib><creatorcontrib>Zhan, Lu</creatorcontrib><creatorcontrib>Han, Jiangbo</creatorcontrib><creatorcontrib>Cai, Tiancai</creatorcontrib><creatorcontrib>Ju, Dianwen</creatorcontrib><creatorcontrib>Feng, Li</creatorcontrib><creatorcontrib>Zhang, Xuyao</creatorcontrib><creatorcontrib>Yin, Kai</creatorcontrib><title>Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer</title><title>Cancer Immunology, Immunotherapy : CII</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Background
CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear.
Methods
The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry.
Results
In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents.
Conclusions
Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Cancer Research</subject><subject>CD47 Antigen</subject><subject>Disease Models, Animal</subject><subject>Flow cytometry</subject><subject>Fusion protein</subject><subject>Gastric cancer</subject><subject>Humans</subject><subject>Immune checkpoint</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Macrophages</subject><subject>Malignancy</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neoplasm Recurrence, Local</subject><subject>Neoplasms</subject><subject>Oncology</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phagocytosis</subject><subject>Stomach Neoplasms</subject><subject>Therapeutic targets</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Xenografts</subject><issn>1432-0851</issn><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kUtP3TAQha2qVaG3_QNdVJa6YRMYP2LHK4RueUlIbNpuLcdxUqNc-2I7SP33Nb2UAgtWtuZ8c2ZGB6HPBA4JgDzKAFTQBihvgAkhG_UG7RPOaqlrydsn_z30IecbAE5Bqfdoj3UtowS6fXS9jk0xaXLFhwmvv3GJTRjwz9PzM-xmb31xA97G4kKpQvFNWTYxYTeOzpaMfcCTySV5i60J1qWP6N1o5uw-Pbwr9OPs9Pv6orm6Pr9cn1w1llNRGjMMjrctF4YIo8zYd6QfieBgOAfGFZWEtbIfiGSCG2hHbiyvNTeAVb1kbIWOd77bpd-4wdb9kpn1NvmNSb91NF4_V4L_pad4pwko0YpqtUIHDw4p3i4uF73x2bp5NsHFJWsGdRFOoBUV_foCvYlLCvU-TVUnBJeMykrRHWVTzDm58XEbAvo-ML0LTNfA9N_AtKpNX57e8djyL6EKsB2QqxQml_7PfsX2D-qen1o</recordid><startdate>20240327</startdate><enddate>20240327</enddate><creator>Zhang, Kaiqi</creator><creator>Xu, Yuan</creator><creator>Chang, Xusheng</creator><creator>Xu, Caili</creator><creator>Xue, Wenjing</creator><creator>Ding, Dan</creator><creator>Nie, Mingming</creator><creator>Cai, Hui</creator><creator>Xu, Jun</creator><creator>Zhan, Lu</creator><creator>Han, Jiangbo</creator><creator>Cai, Tiancai</creator><creator>Ju, Dianwen</creator><creator>Feng, Li</creator><creator>Zhang, Xuyao</creator><creator>Yin, Kai</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><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>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20240327</creationdate><title>Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer</title><author>Zhang, Kaiqi ; Xu, Yuan ; Chang, Xusheng ; Xu, Caili ; Xue, Wenjing ; Ding, Dan ; Nie, Mingming ; Cai, Hui ; Xu, Jun ; Zhan, Lu ; Han, Jiangbo ; Cai, Tiancai ; Ju, Dianwen ; Feng, Li ; Zhang, Xuyao ; Yin, Kai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-adde45546a16a9afb81bf1640a440349271357bd17364a05f4ac4713ed0c9b733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Cancer Research</topic><topic>CD47 Antigen</topic><topic>Disease Models, Animal</topic><topic>Flow cytometry</topic><topic>Fusion protein</topic><topic>Gastric cancer</topic><topic>Humans</topic><topic>Immune checkpoint</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Leukocytes (mononuclear)</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Macrophages</topic><topic>Malignancy</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neoplasm Recurrence, Local</topic><topic>Neoplasms</topic><topic>Oncology</topic><topic>Patients</topic><topic>Peripheral blood mononuclear cells</topic><topic>Phagocytosis</topic><topic>Stomach Neoplasms</topic><topic>Therapeutic targets</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Kaiqi</creatorcontrib><creatorcontrib>Xu, Yuan</creatorcontrib><creatorcontrib>Chang, Xusheng</creatorcontrib><creatorcontrib>Xu, Caili</creatorcontrib><creatorcontrib>Xue, Wenjing</creatorcontrib><creatorcontrib>Ding, Dan</creatorcontrib><creatorcontrib>Nie, Mingming</creatorcontrib><creatorcontrib>Cai, Hui</creatorcontrib><creatorcontrib>Xu, Jun</creatorcontrib><creatorcontrib>Zhan, Lu</creatorcontrib><creatorcontrib>Han, Jiangbo</creatorcontrib><creatorcontrib>Cai, Tiancai</creatorcontrib><creatorcontrib>Ju, Dianwen</creatorcontrib><creatorcontrib>Feng, Li</creatorcontrib><creatorcontrib>Zhang, Xuyao</creatorcontrib><creatorcontrib>Yin, Kai</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy : CII</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Kaiqi</au><au>Xu, Yuan</au><au>Chang, Xusheng</au><au>Xu, Caili</au><au>Xue, Wenjing</au><au>Ding, Dan</au><au>Nie, Mingming</au><au>Cai, Hui</au><au>Xu, Jun</au><au>Zhan, Lu</au><au>Han, Jiangbo</au><au>Cai, Tiancai</au><au>Ju, Dianwen</au><au>Feng, Li</au><au>Zhang, Xuyao</au><au>Yin, Kai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer</atitle><jtitle>Cancer Immunology, Immunotherapy : CII</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2024-03-27</date><risdate>2024</risdate><volume>73</volume><issue>4</issue><spage>75</spage><pages>75-</pages><artnum>75</artnum><issn>1432-0851</issn><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Background
CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear.
Methods
The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry.
Results
In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents.
Conclusions
Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>38532108</pmid><doi>10.1007/s00262-024-03667-9</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Animals Cancer Research CD47 Antigen Disease Models, Animal Flow cytometry Fusion protein Gastric cancer Humans Immune checkpoint Immunohistochemistry Immunology Immunotherapy Leukocytes (mononuclear) Leukocytes, Mononuclear - metabolism Macrophages Malignancy Medical prognosis Medicine Medicine & Public Health Neoplasm Recurrence, Local Neoplasms Oncology Patients Peripheral blood mononuclear cells Phagocytosis Stomach Neoplasms Therapeutic targets Tumors Vascular endothelial growth factor Vascular Endothelial Growth Factor A Xenografts |
| title | Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer |
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