PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer
Immune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition. Whole blood was collected at serial timepoints from metastat...
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| creator | Darga, Elizabeth P Dolce, Emily M Fang, Fang Kidwell, Kelley M Gersch, Christina L Kregel, Steven Thomas, Dafydd G Gill, Anoop Brown, Martha E Gross, Steven Connelly, Mark Holinstat, Michael Cobain, Erin F Rae, James M Hayes, Daniel F Paoletti, Costanza |
| description | Immune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition.
Whole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1.
A total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p |
| doi_str_mv | 10.1371/journal.pone.0260124 |
| format | Article |
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Whole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1.
A total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p<0.001) and a history of smoking tobacco (OR = 0.76, p<0.001). Platelet PD-L1 staining was not associated with tumor marker status, recent procedures or treatments, platelet-affecting drugs, or CTC PD-L1 expression.
PD-L1 expression was found in metastatic breast cancer patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0260124</identifier><identifier>PMID: 34780566</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antigens ; Apoptosis ; B7-H1 Antigen - genetics ; B7-H1 Antigen - metabolism ; Biology and Life Sciences ; Biomarkers ; Blood ; Blood platelets ; Blood Platelets - metabolism ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Case-Control Studies ; Cell Line, Tumor ; Diagnosis ; Effector cells ; Erythrocytes ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genetic aspects ; Humans ; Immune checkpoint ; Immune checkpoint inhibitors ; Immunosuppressive agents ; Internal medicine ; MCF-7 Cells ; Medical schools ; Medicine ; Medicine and Health Sciences ; Metastases ; Metastasis ; Monoclonal antibodies ; Neoplasm Metastasis ; Neoplastic Cells, Circulating - metabolism ; Oncology ; Patients ; PD-L1 protein ; Pharmacodynamics ; Platelets ; Public health ; Red blood cells ; Research and Analysis Methods ; Software ; Supervision ; Tobacco ; Tumor cells ; Tumor markers ; Tumors ; Up-Regulation</subject><ispartof>PloS one, 2021-11, Vol.16 (11), p.e0260124-e0260124</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Darga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Darga et al 2021 Darga et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5a1a7b1131904a30bd38716a181e82146cf759405cf12d9fb606e8de19d30df53</citedby><cites>FETCH-LOGICAL-c692t-5a1a7b1131904a30bd38716a181e82146cf759405cf12d9fb606e8de19d30df53</cites><orcidid>0000-0002-1717-4483 ; 0000-0001-7212-8116 ; 0000-0001-5100-1933</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592410/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592410/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34780566$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Heymann, Dominique</contributor><creatorcontrib>Darga, Elizabeth P</creatorcontrib><creatorcontrib>Dolce, Emily M</creatorcontrib><creatorcontrib>Fang, Fang</creatorcontrib><creatorcontrib>Kidwell, Kelley M</creatorcontrib><creatorcontrib>Gersch, Christina L</creatorcontrib><creatorcontrib>Kregel, Steven</creatorcontrib><creatorcontrib>Thomas, Dafydd G</creatorcontrib><creatorcontrib>Gill, Anoop</creatorcontrib><creatorcontrib>Brown, Martha E</creatorcontrib><creatorcontrib>Gross, Steven</creatorcontrib><creatorcontrib>Connelly, Mark</creatorcontrib><creatorcontrib>Holinstat, Michael</creatorcontrib><creatorcontrib>Cobain, Erin F</creatorcontrib><creatorcontrib>Rae, James M</creatorcontrib><creatorcontrib>Hayes, Daniel F</creatorcontrib><creatorcontrib>Paoletti, Costanza</creatorcontrib><title>PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Immune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition.
Whole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1.
A total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p<0.001) and a history of smoking tobacco (OR = 0.76, p<0.001). Platelet PD-L1 staining was not associated with tumor marker status, recent procedures or treatments, platelet-affecting drugs, or CTC PD-L1 expression.
PD-L1 expression was found in metastatic breast cancer patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment.</description><subject>Analysis</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>B7-H1 Antigen - genetics</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>Blood platelets</subject><subject>Blood Platelets - metabolism</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Case-Control Studies</subject><subject>Cell Line, Tumor</subject><subject>Diagnosis</subject><subject>Effector cells</subject><subject>Erythrocytes</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Knockdown Techniques</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Immune checkpoint</subject><subject>Immune checkpoint inhibitors</subject><subject>Immunosuppressive agents</subject><subject>Internal medicine</subject><subject>MCF-7 Cells</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Monoclonal antibodies</subject><subject>Neoplasm Metastasis</subject><subject>Neoplastic Cells, Circulating - metabolism</subject><subject>Oncology</subject><subject>Patients</subject><subject>PD-L1 protein</subject><subject>Pharmacodynamics</subject><subject>Platelets</subject><subject>Public health</subject><subject>Red blood cells</subject><subject>Research and Analysis Methods</subject><subject>Software</subject><subject>Supervision</subject><subject>Tobacco</subject><subject>Tumor cells</subject><subject>Tumor markers</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk22L1DAQx4so3nn6DUQLguiLXfPUNH0jHOfTwsKJT29Dmk53s6RNL0n1_PZm3d6xlXshDXSY_OafyWQmy55itMS0xG92bvS9ssvB9bBEhCNM2L3sFFeULDhB9P6RfZI9CmGHUEEF5w-zE8pKgQrOTzP9-d1ijXO4HjyEYFyfp6WN16NV0fSbPI6d87kGa0Ou-iYfkh8sxJCbPh8SA32yf5m4zTuIKsTk0nntIZm5Vr0G_zh70Cob4Mn0P8u-f3j_7eLTYn35cXVxvl5oXpG4KBRWZY0xxRViiqK6oaLEXGGBQRDMuG7LomKo0C0mTdXWHHEQDeCqoahpC3qWPT_oDtYFOdUnSFJUAlFGEUrE6kA0Tu3k4E2n_G_plJF_Hc5vpPIpfwuSiBYwbVqsCWNE1zXiqBEI6lK3pGYsab2dThvrDhqd6uCVnYnOd3qzlRv3U4qiIgzvk3k1CXh3NUKIsjNhX2jVgxunvEtBqEjoi3_Qu283URuVLmD61qVz9V5UnnNBihIjghO1vINKXwOd0amZWpP8s4DXs4DERLiOGzWGIFdfv_w_e_ljzr48YregbNwGZ8eYujDMQXYAtXcheGhvi4yR3M_CTTXkfhbkNAsp7NnxA90G3TQ__QM86gOO</recordid><startdate>20211115</startdate><enddate>20211115</enddate><creator>Darga, Elizabeth P</creator><creator>Dolce, Emily M</creator><creator>Fang, Fang</creator><creator>Kidwell, Kelley M</creator><creator>Gersch, Christina L</creator><creator>Kregel, Steven</creator><creator>Thomas, Dafydd G</creator><creator>Gill, Anoop</creator><creator>Brown, Martha E</creator><creator>Gross, Steven</creator><creator>Connelly, Mark</creator><creator>Holinstat, Michael</creator><creator>Cobain, Erin F</creator><creator>Rae, James M</creator><creator>Hayes, Daniel F</creator><creator>Paoletti, Costanza</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1717-4483</orcidid><orcidid>https://orcid.org/0000-0001-7212-8116</orcidid><orcidid>https://orcid.org/0000-0001-5100-1933</orcidid></search><sort><creationdate>20211115</creationdate><title>PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer</title><author>Darga, Elizabeth P ; Dolce, Emily M ; Fang, Fang ; Kidwell, Kelley M ; Gersch, Christina L ; Kregel, Steven ; Thomas, Dafydd G ; Gill, Anoop ; Brown, Martha E ; Gross, Steven ; Connelly, Mark ; Holinstat, Michael ; Cobain, Erin F ; Rae, James M ; Hayes, Daniel F ; Paoletti, Costanza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-5a1a7b1131904a30bd38716a181e82146cf759405cf12d9fb606e8de19d30df53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Antigens</topic><topic>Apoptosis</topic><topic>B7-H1 Antigen - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Darga, Elizabeth P</au><au>Dolce, Emily M</au><au>Fang, Fang</au><au>Kidwell, Kelley M</au><au>Gersch, Christina L</au><au>Kregel, Steven</au><au>Thomas, Dafydd G</au><au>Gill, Anoop</au><au>Brown, Martha E</au><au>Gross, Steven</au><au>Connelly, Mark</au><au>Holinstat, Michael</au><au>Cobain, Erin F</au><au>Rae, James M</au><au>Hayes, Daniel F</au><au>Paoletti, Costanza</au><au>Heymann, Dominique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-11-15</date><risdate>2021</risdate><volume>16</volume><issue>11</issue><spage>e0260124</spage><epage>e0260124</epage><pages>e0260124-e0260124</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Immune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition.
Whole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1.
A total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p<0.001) and a history of smoking tobacco (OR = 0.76, p<0.001). Platelet PD-L1 staining was not associated with tumor marker status, recent procedures or treatments, platelet-affecting drugs, or CTC PD-L1 expression.
PD-L1 expression was found in metastatic breast cancer patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34780566</pmid><doi>10.1371/journal.pone.0260124</doi><tpages>e0260124</tpages><orcidid>https://orcid.org/0000-0002-1717-4483</orcidid><orcidid>https://orcid.org/0000-0001-7212-8116</orcidid><orcidid>https://orcid.org/0000-0001-5100-1933</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-11, Vol.16 (11), p.e0260124-e0260124 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2598034300 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Antigens Apoptosis B7-H1 Antigen - genetics B7-H1 Antigen - metabolism Biology and Life Sciences Biomarkers Blood Blood platelets Blood Platelets - metabolism Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Case-Control Studies Cell Line, Tumor Diagnosis Effector cells Erythrocytes Female Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Genetic aspects Humans Immune checkpoint Immune checkpoint inhibitors Immunosuppressive agents Internal medicine MCF-7 Cells Medical schools Medicine Medicine and Health Sciences Metastases Metastasis Monoclonal antibodies Neoplasm Metastasis Neoplastic Cells, Circulating - metabolism Oncology Patients PD-L1 protein Pharmacodynamics Platelets Public health Red blood cells Research and Analysis Methods Software Supervision Tobacco Tumor cells Tumor markers Tumors Up-Regulation |
| title | PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer |
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