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Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer
In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochem...
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| Published in: | Cancer Immunology, Immunotherapy Immunotherapy, 2017-07, Vol.66 (7), p.927-939 |
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| container_end_page | 939 |
| container_issue | 7 |
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| container_title | Cancer Immunology, Immunotherapy |
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| creator | Lee, Kyu Sang Kwak, Yoonjin Ahn, Soyeon Shin, Eun Oh, Heung-Kwon Kim, Duck-Woo Kang, Sung-Bum Choe, Gheeyoung Kim, Woo Ho Lee, Hye Seung |
| description | In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC. IHC slides stained for CD3 and CD8 were scanned using an Aperio ScanScope for precise calculation of tumor-infiltrating T cell density. Additionally, samples were screened for the B-Raf (BRAF)-V600E mutation using a Cobas 4800 System and IHC. In total, CD274
TC
, CD274
TP
, CD274
IC
, and CD274
IP
were observed in 43 (23.1%), 47 (25.3%), 107 (57.5%), and 102 (54.8%) of the MSI-H CRCs examined, and in three (2.0%), four (2.6%), 47 (30.7%), and 56 (36.6%) of the 153 MSS CRCs tested. Meanwhile, intratumoral heterogeneity of CD274 expression in tumor cells and immune cells was detected in 24 (12.9%) and 47 (25.3%) MSI-H CRCs, respectively. Notably, in both MSI-H and MSS CRC, CD274
IC
and CD274
IP
were independently associated with improved prognosis (
P
|
| doi_str_mv | 10.1007/s00262-017-1999-6 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11028600</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1887424295</sourcerecordid><originalsourceid>FETCH-LOGICAL-c494t-236125754089e6b25d9d415575fc743cc2a48549f10ef65e290d0f3215b0f84b3</originalsourceid><addsrcrecordid>eNp1kcGOFCEURYnROD2jH-DGkLgZF6UPCqhiZUyPoyadOAtdE4qClkkVtEAZ_RG_VyrdTkYTV8B75124XISeEXhFALrXGYAK2gDpGiKlbMQDtCGsrZWek4doAy2DpgNgZ-g859u6oSDlY3RGewa8E2yDft2kuA8xF2-wnw-TN7r4GHB0eHtFO4Yvb66aHXmJDykW6wO2Pw7J5rwy9VSWOabGB-enkupk2FeVeQkWGztNGbuY8OxNilmXWvDF4iXkoofJYh1GfNqaOMVkTdETNjoYm56gR05P2T49rRfoy_W7z9sPze7T-4_bt7vGMMlKQ1tBKO84g15aMVA-ypERXivOdKw1hmrWcyYdAesEt1TCCK6lhA_geja0F-jNUfewDLMdjQ3VxqQOyc86_VRRe_V3J_ivah-_K0KA9gKgKlyeFFL8tthc1Ozzal4HG5esSN93jDIqeUVf_IPexiWF6k8RSRhjUoiuUuRIrb-Wk3V3ryGg1tjVMXZVY1dr7ErUmef3bdxN_Mm5AvQI5NoKe5vuXf1f1d_5-7nA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1914449667</pqid></control><display><type>article</type><title>Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer</title><source>NCBI_PubMed Central（免费）</source><source>Springer Link</source><creator>Lee, Kyu Sang ; Kwak, Yoonjin ; Ahn, Soyeon ; Shin, Eun ; Oh, Heung-Kwon ; Kim, Duck-Woo ; Kang, Sung-Bum ; Choe, Gheeyoung ; Kim, Woo Ho ; Lee, Hye Seung</creator><creatorcontrib>Lee, Kyu Sang ; Kwak, Yoonjin ; Ahn, Soyeon ; Shin, Eun ; Oh, Heung-Kwon ; Kim, Duck-Woo ; Kang, Sung-Bum ; Choe, Gheeyoung ; Kim, Woo Ho ; Lee, Hye Seung</creatorcontrib><description>In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC. IHC slides stained for CD3 and CD8 were scanned using an Aperio ScanScope for precise calculation of tumor-infiltrating T cell density. Additionally, samples were screened for the B-Raf (BRAF)-V600E mutation using a Cobas 4800 System and IHC. In total, CD274
TC
, CD274
TP
, CD274
IC
, and CD274
IP
were observed in 43 (23.1%), 47 (25.3%), 107 (57.5%), and 102 (54.8%) of the MSI-H CRCs examined, and in three (2.0%), four (2.6%), 47 (30.7%), and 56 (36.6%) of the 153 MSS CRCs tested. Meanwhile, intratumoral heterogeneity of CD274 expression in tumor cells and immune cells was detected in 24 (12.9%) and 47 (25.3%) MSI-H CRCs, respectively. Notably, in both MSI-H and MSS CRC, CD274
IC
and CD274
IP
were independently associated with improved prognosis (
P
< 0.05), while
BRAF
mutation was associated with CD274
TP
, poor differentiation, sporadic type, and hMLH1(−)/hMSH2(+)/hMSH6(+)/PMS2(−) in MSI-H CRC (
P
< 0.006). In conclusion, CD274 expression in tumor-infiltrating immune cells was an independent factor for improved prognosis in CRC patients. A deeper understanding of CD274 status may yield improved responses to future CRC immunotherapies.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-017-1999-6</identifier><identifier>PMID: 28405764</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Aged ; B7-H1 Antigen - genetics ; B7-H1 Antigen - metabolism ; Cancer Research ; CD3 antigen ; CD3 Complex - biosynthesis ; CD8 antigen ; CD8 Antigens - biosynthesis ; Cell density ; Cohort Studies ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - diagnosis ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Female ; Genetic Markers ; Heterogeneity ; Humans ; Immunohistochemistry ; Immunology ; Immunotherapy ; Kaplan-Meier Estimate ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - metabolism ; Male ; Medicine ; Medicine & Public Health ; Microsatellite Instability ; Microsatellite Repeats ; Middle Aged ; Mismatch repair ; Mutation ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Oncology ; Original ; Original Article ; PD-L1 protein ; Prognosis ; Protein expression ; Proteins ; Proto-Oncogene Proteins B-raf - genetics ; Proto-Oncogene Proteins B-raf - metabolism ; Raf protein ; Tissue Array Analysis ; Tumor cells ; Tumor-infiltrating lymphocytes</subject><ispartof>Cancer Immunology, Immunotherapy, 2017-07, Vol.66 (7), p.927-939</ispartof><rights>Springer-Verlag Berlin Heidelberg 2017</rights><rights>Cancer Immunology, Immunotherapy is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-236125754089e6b25d9d415575fc743cc2a48549f10ef65e290d0f3215b0f84b3</citedby><cites>FETCH-LOGICAL-c494t-236125754089e6b25d9d415575fc743cc2a48549f10ef65e290d0f3215b0f84b3</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/PMC11028600/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11028600/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28405764$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Kyu Sang</creatorcontrib><creatorcontrib>Kwak, Yoonjin</creatorcontrib><creatorcontrib>Ahn, Soyeon</creatorcontrib><creatorcontrib>Shin, Eun</creatorcontrib><creatorcontrib>Oh, Heung-Kwon</creatorcontrib><creatorcontrib>Kim, Duck-Woo</creatorcontrib><creatorcontrib>Kang, Sung-Bum</creatorcontrib><creatorcontrib>Choe, Gheeyoung</creatorcontrib><creatorcontrib>Kim, Woo Ho</creatorcontrib><creatorcontrib>Lee, Hye Seung</creatorcontrib><title>Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC. IHC slides stained for CD3 and CD8 were scanned using an Aperio ScanScope for precise calculation of tumor-infiltrating T cell density. Additionally, samples were screened for the B-Raf (BRAF)-V600E mutation using a Cobas 4800 System and IHC. In total, CD274
TC
, CD274
TP
, CD274
IC
, and CD274
IP
were observed in 43 (23.1%), 47 (25.3%), 107 (57.5%), and 102 (54.8%) of the MSI-H CRCs examined, and in three (2.0%), four (2.6%), 47 (30.7%), and 56 (36.6%) of the 153 MSS CRCs tested. Meanwhile, intratumoral heterogeneity of CD274 expression in tumor cells and immune cells was detected in 24 (12.9%) and 47 (25.3%) MSI-H CRCs, respectively. Notably, in both MSI-H and MSS CRC, CD274
IC
and CD274
IP
were independently associated with improved prognosis (
P
< 0.05), while
BRAF
mutation was associated with CD274
TP
, poor differentiation, sporadic type, and hMLH1(−)/hMSH2(+)/hMSH6(+)/PMS2(−) in MSI-H CRC (
P
< 0.006). In conclusion, CD274 expression in tumor-infiltrating immune cells was an independent factor for improved prognosis in CRC patients. A deeper understanding of CD274 status may yield improved responses to future CRC immunotherapies.</description><subject>Aged</subject><subject>B7-H1 Antigen - genetics</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Cancer Research</subject><subject>CD3 antigen</subject><subject>CD3 Complex - biosynthesis</subject><subject>CD8 antigen</subject><subject>CD8 Antigens - biosynthesis</subject><subject>Cell density</subject><subject>Cohort Studies</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - diagnosis</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Female</subject><subject>Genetic Markers</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Kaplan-Meier Estimate</subject><subject>Lymphocytes T</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - metabolism</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Microsatellite Instability</subject><subject>Microsatellite Repeats</subject><subject>Middle Aged</subject><subject>Mismatch repair</subject><subject>Mutation</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>PD-L1 protein</subject><subject>Prognosis</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Proto-Oncogene Proteins B-raf - metabolism</subject><subject>Raf protein</subject><subject>Tissue Array Analysis</subject><subject>Tumor cells</subject><subject>Tumor-infiltrating lymphocytes</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp1kcGOFCEURYnROD2jH-DGkLgZF6UPCqhiZUyPoyadOAtdE4qClkkVtEAZ_RG_VyrdTkYTV8B75124XISeEXhFALrXGYAK2gDpGiKlbMQDtCGsrZWek4doAy2DpgNgZ-g859u6oSDlY3RGewa8E2yDft2kuA8xF2-wnw-TN7r4GHB0eHtFO4Yvb66aHXmJDykW6wO2Pw7J5rwy9VSWOabGB-enkupk2FeVeQkWGztNGbuY8OxNilmXWvDF4iXkoofJYh1GfNqaOMVkTdETNjoYm56gR05P2T49rRfoy_W7z9sPze7T-4_bt7vGMMlKQ1tBKO84g15aMVA-ypERXivOdKw1hmrWcyYdAesEt1TCCK6lhA_geja0F-jNUfewDLMdjQ3VxqQOyc86_VRRe_V3J_ivah-_K0KA9gKgKlyeFFL8tthc1Ozzal4HG5esSN93jDIqeUVf_IPexiWF6k8RSRhjUoiuUuRIrb-Wk3V3ryGg1tjVMXZVY1dr7ErUmef3bdxN_Mm5AvQI5NoKe5vuXf1f1d_5-7nA</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Lee, Kyu Sang</creator><creator>Kwak, Yoonjin</creator><creator>Ahn, Soyeon</creator><creator>Shin, Eun</creator><creator>Oh, Heung-Kwon</creator><creator>Kim, Duck-Woo</creator><creator>Kang, Sung-Bum</creator><creator>Choe, Gheeyoung</creator><creator>Kim, Woo Ho</creator><creator>Lee, Hye Seung</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170701</creationdate><title>Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer</title><author>Lee, Kyu Sang ; Kwak, Yoonjin ; Ahn, Soyeon ; Shin, Eun ; Oh, Heung-Kwon ; Kim, Duck-Woo ; Kang, Sung-Bum ; Choe, Gheeyoung ; Kim, Woo Ho ; Lee, Hye Seung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-236125754089e6b25d9d415575fc743cc2a48549f10ef65e290d0f3215b0f84b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>B7-H1 Antigen - genetics</topic><topic>B7-H1 Antigen - metabolism</topic><topic>Cancer Research</topic><topic>CD3 antigen</topic><topic>CD3 Complex - biosynthesis</topic><topic>CD8 antigen</topic><topic>CD8 Antigens - biosynthesis</topic><topic>Cell density</topic><topic>Cohort Studies</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - diagnosis</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Female</topic><topic>Genetic Markers</topic><topic>Heterogeneity</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Kaplan-Meier Estimate</topic><topic>Lymphocytes T</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - metabolism</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Microsatellite Instability</topic><topic>Microsatellite Repeats</topic><topic>Middle Aged</topic><topic>Mismatch repair</topic><topic>Mutation</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>PD-L1 protein</topic><topic>Prognosis</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Proto-Oncogene Proteins B-raf - metabolism</topic><topic>Raf protein</topic><topic>Tissue Array Analysis</topic><topic>Tumor cells</topic><topic>Tumor-infiltrating lymphocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Kyu Sang</creatorcontrib><creatorcontrib>Kwak, Yoonjin</creatorcontrib><creatorcontrib>Ahn, Soyeon</creatorcontrib><creatorcontrib>Shin, Eun</creatorcontrib><creatorcontrib>Oh, Heung-Kwon</creatorcontrib><creatorcontrib>Kim, Duck-Woo</creatorcontrib><creatorcontrib>Kang, Sung-Bum</creatorcontrib><creatorcontrib>Choe, Gheeyoung</creatorcontrib><creatorcontrib>Kim, Woo Ho</creatorcontrib><creatorcontrib>Lee, Hye Seung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Kyu Sang</au><au>Kwak, Yoonjin</au><au>Ahn, Soyeon</au><au>Shin, Eun</au><au>Oh, Heung-Kwon</au><au>Kim, Duck-Woo</au><au>Kang, Sung-Bum</au><au>Choe, Gheeyoung</au><au>Kim, Woo Ho</au><au>Lee, Hye Seung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2017-07-01</date><risdate>2017</risdate><volume>66</volume><issue>7</issue><spage>927</spage><epage>939</epage><pages>927-939</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC. IHC slides stained for CD3 and CD8 were scanned using an Aperio ScanScope for precise calculation of tumor-infiltrating T cell density. Additionally, samples were screened for the B-Raf (BRAF)-V600E mutation using a Cobas 4800 System and IHC. In total, CD274
TC
, CD274
TP
, CD274
IC
, and CD274
IP
were observed in 43 (23.1%), 47 (25.3%), 107 (57.5%), and 102 (54.8%) of the MSI-H CRCs examined, and in three (2.0%), four (2.6%), 47 (30.7%), and 56 (36.6%) of the 153 MSS CRCs tested. Meanwhile, intratumoral heterogeneity of CD274 expression in tumor cells and immune cells was detected in 24 (12.9%) and 47 (25.3%) MSI-H CRCs, respectively. Notably, in both MSI-H and MSS CRC, CD274
IC
and CD274
IP
were independently associated with improved prognosis (
P
< 0.05), while
BRAF
mutation was associated with CD274
TP
, poor differentiation, sporadic type, and hMLH1(−)/hMSH2(+)/hMSH6(+)/PMS2(−) in MSI-H CRC (
P
< 0.006). In conclusion, CD274 expression in tumor-infiltrating immune cells was an independent factor for improved prognosis in CRC patients. A deeper understanding of CD274 status may yield improved responses to future CRC immunotherapies.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>28405764</pmid><doi>10.1007/s00262-017-1999-6</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-7004 |
| ispartof | Cancer Immunology, Immunotherapy, 2017-07, Vol.66 (7), p.927-939 |
| issn | 0340-7004 1432-0851 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11028600 |
| source | NCBI_PubMed Central（免费）; Springer Link |
| subjects | Aged B7-H1 Antigen - genetics B7-H1 Antigen - metabolism Cancer Research CD3 antigen CD3 Complex - biosynthesis CD8 antigen CD8 Antigens - biosynthesis Cell density Cohort Studies Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - diagnosis Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Female Genetic Markers Heterogeneity Humans Immunohistochemistry Immunology Immunotherapy Kaplan-Meier Estimate Lymphocytes T Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism Male Medicine Medicine & Public Health Microsatellite Instability Microsatellite Repeats Middle Aged Mismatch repair Mutation Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Oncology Original Original Article PD-L1 protein Prognosis Protein expression Proteins Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins B-raf - metabolism Raf protein Tissue Array Analysis Tumor cells Tumor-infiltrating lymphocytes |
| title | Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T13%3A10%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prognostic%20implication%20of%20CD274%20(PD-L1)%20protein%20expression%20in%20tumor-infiltrating%20immune%20cells%20for%20microsatellite%20unstable%20and%20stable%20colorectal%20cancer&rft.jtitle=Cancer%20Immunology,%20Immunotherapy&rft.au=Lee,%20Kyu%20Sang&rft.date=2017-07-01&rft.volume=66&rft.issue=7&rft.spage=927&rft.epage=939&rft.pages=927-939&rft.issn=0340-7004&rft.eissn=1432-0851&rft_id=info:doi/10.1007/s00262-017-1999-6&rft_dat=%3Cproquest_pubme%3E1887424295%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c494t-236125754089e6b25d9d415575fc743cc2a48549f10ef65e290d0f3215b0f84b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1914449667&rft_id=info:pmid/28405764&rfr_iscdi=true |