Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact
Downregulation of human leukocyte antigen (HLA) class I has been postulated to be a mechanism of adaptive immune escape in various tumors, especially microsatellite instability–high (MSI‐H) colorectal cancer (CRC). In this study, we aimed to investigate HLA class I and β2‐microglobulin (β2M) express...
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| Veröffentlicht in: | Cancer science 2021-01, Vol.112 (1), p.91-100 |
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| creator | Na, Hee Young Park, Yujun Nam, Soo Kyung Lee, Kyu Sang Oh, Heung‐Kwon Kim, Duck‐Woo Kang, Sung‐Bum Kim, Woo Ho Lee, Hye Seung |
| description | Downregulation of human leukocyte antigen (HLA) class I has been postulated to be a mechanism of adaptive immune escape in various tumors, especially microsatellite instability–high (MSI‐H) colorectal cancer (CRC). In this study, we aimed to investigate HLA class I and β2‐microglobulin (β2M) expression in MSI‐H and microsatellite‐stable (MSS) CRCs and determine its prognostic impact. The representative areas from the tumor center (TC) and tumor periphery (TP) from 300 CRCs, including 161 MSI‐H and 139 MSS cases, were selected to construct a tissue microarray. Immunohistochemistry (IHC) for HLA A/B/C, β2M, CD3, and CD8 was performed. Reduced HLA A/B/C expression was detected in 113 (70.2%) MSI‐H and 54 (38.8%) MSS cases, while reduced β2M expression was observed in 69 (42.9%) MSI‐H and 17 (12.2%) MSS cases. Although reduced β2M expression was associated with higher pathological tumor (pT) stage in MSI‐H CRC with borderline significance, no association was found between HLA A/B/C and β2M expression and survival. Interestingly, reduced HLA A/B/C expression in MSS was associated with higher stage, and reduced HLA A/B/C and β2M expression was an independent prognostic factor in multivariate analysis. In conclusion, reduced HLA A/B/C and β2M expression was frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitor. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor prognosis in MSS cancers. Overall, IHC for HLA A/B/C and β2M might be a feasible predictive or prognostic tool in CRC.
Reduced HLA A/B/C and β2M expression is frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitors. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor survival in MSS cancers, but not in MSI‐H tumors, indicating that cell‐mediated antitumoral immune response may also play an important role in MSS CRC. Together, IHC for HLA A/B/C and β2M can be a predictive or prognostic tool in CRC. |
| doi_str_mv | 10.1111/cas.14723 |
| format | Article |
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Reduced HLA A/B/C and β2M expression is frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitors. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor survival in MSS cancers, but not in MSI‐H tumors, indicating that cell‐mediated antitumoral immune response may also play an important role in MSS CRC. Together, IHC for HLA A/B/C and β2M can be a predictive or prognostic tool in CRC.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.14723</identifier><identifier>PMID: 33159376</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens ; Basic and Clinical Immunology ; beta 2-Microglobulin - genetics ; CD3 antigen ; CD8 antigen ; Chemotherapy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Down-Regulation - genetics ; Female ; Histocompatibility antigen HLA ; Histocompatibility Antigens Class I - genetics ; human leukocyte antigen class I ; Humans ; Immune checkpoint inhibitors ; Immunohistochemistry ; Immunohistochemistry - methods ; Immunotherapy ; Lung cancer ; Lymphocytes ; Male ; Medical prognosis ; Medical research ; Microsatellite Instability ; Microsatellite Repeats - genetics ; Middle Aged ; Multivariate analysis ; Mutation ; Original ; Patients ; Prognosis ; Statistical analysis ; Tumors ; Young Adult ; β2‐microglobulin</subject><ispartof>Cancer science, 2021-01, Vol.112 (1), p.91-100</ispartof><rights>2020 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association</rights><rights>2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by-nc/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><citedby>FETCH-LOGICAL-c4673-7ff560c6908bf0a547a8e4b7fa2a430c2e64d32dbebb57b3d99c6ad0cf6ccc673</citedby><cites>FETCH-LOGICAL-c4673-7ff560c6908bf0a547a8e4b7fa2a430c2e64d32dbebb57b3d99c6ad0cf6ccc673</cites><orcidid>0000-0002-1667-7986</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/PMC7780028/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780028/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33159376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Na, Hee Young</creatorcontrib><creatorcontrib>Park, Yujun</creatorcontrib><creatorcontrib>Nam, Soo Kyung</creatorcontrib><creatorcontrib>Lee, Kyu Sang</creatorcontrib><creatorcontrib>Oh, Heung‐Kwon</creatorcontrib><creatorcontrib>Kim, Duck‐Woo</creatorcontrib><creatorcontrib>Kang, Sung‐Bum</creatorcontrib><creatorcontrib>Kim, Woo Ho</creatorcontrib><creatorcontrib>Lee, Hye Seung</creatorcontrib><title>Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Downregulation of human leukocyte antigen (HLA) class I has been postulated to be a mechanism of adaptive immune escape in various tumors, especially microsatellite instability–high (MSI‐H) colorectal cancer (CRC). In this study, we aimed to investigate HLA class I and β2‐microglobulin (β2M) expression in MSI‐H and microsatellite‐stable (MSS) CRCs and determine its prognostic impact. The representative areas from the tumor center (TC) and tumor periphery (TP) from 300 CRCs, including 161 MSI‐H and 139 MSS cases, were selected to construct a tissue microarray. Immunohistochemistry (IHC) for HLA A/B/C, β2M, CD3, and CD8 was performed. Reduced HLA A/B/C expression was detected in 113 (70.2%) MSI‐H and 54 (38.8%) MSS cases, while reduced β2M expression was observed in 69 (42.9%) MSI‐H and 17 (12.2%) MSS cases. Although reduced β2M expression was associated with higher pathological tumor (pT) stage in MSI‐H CRC with borderline significance, no association was found between HLA A/B/C and β2M expression and survival. Interestingly, reduced HLA A/B/C expression in MSS was associated with higher stage, and reduced HLA A/B/C and β2M expression was an independent prognostic factor in multivariate analysis. In conclusion, reduced HLA A/B/C and β2M expression was frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitor. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor prognosis in MSS cancers. Overall, IHC for HLA A/B/C and β2M might be a feasible predictive or prognostic tool in CRC.
Reduced HLA A/B/C and β2M expression is frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitors. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor survival in MSS cancers, but not in MSI‐H tumors, indicating that cell‐mediated antitumoral immune response may also play an important role in MSS CRC. Together, IHC for HLA A/B/C and β2M can be a predictive or prognostic tool in CRC.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens</subject><subject>Basic and Clinical Immunology</subject><subject>beta 2-Microglobulin - genetics</subject><subject>CD3 antigen</subject><subject>CD8 antigen</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Down-Regulation - genetics</subject><subject>Female</subject><subject>Histocompatibility antigen HLA</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>human leukocyte antigen class I</subject><subject>Humans</subject><subject>Immune checkpoint inhibitors</subject><subject>Immunohistochemistry</subject><subject>Immunohistochemistry - methods</subject><subject>Immunotherapy</subject><subject>Lung cancer</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Microsatellite Instability</subject><subject>Microsatellite Repeats - genetics</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Mutation</subject><subject>Original</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Statistical analysis</subject><subject>Tumors</subject><subject>Young Adult</subject><subject>β2‐microglobulin</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kc9qFTEUhwex2Fpd-AIScKOLafNvkpmNUC7VFgou1HXInMncpmaSMclU785H8Fl8EB_CJ2l6by0qGA4kh3x8nORXVc8IPiJlHYNOR4RLyh5UB4TxrpYYi4fbs6w7zOh-9TilK4yZ4B1_VO0zRpqOSXFQ5dOvczQp2eBRGNHlMmmPnFk-Bdhkg7TPdm08AqdTQuelH9DPH_TXt--ThRjWLvSLsx6VguBCNJC1Q6A9mLiFbU5oLqAPKVtAdpo15CfV3qhdMk_v9sPq45vTD6uz-uLd2_PVyUUNXEhWy3FsBAbR4bYfsW641K3hvRw11ZxhoEbwgdGhN33fyJ4NXQdCDxhGAQDFcFi93nnnpZ_MAMbnqJ2ao5103Kigrfr7xttLtQ7XSsoWY9oWwcs7QQyfF5OymmwC45z2JixJUd60knSM8IK--Ae9Ckv05XmFklyKjkpSqFc7qnxeStGM98MQrG6zVCVLtc2ysM__nP6e_B1eAY53wBfrzOb_JrU6eb9T3gBVr60v</recordid><startdate>202101</startdate><enddate>202101</enddate><creator>Na, Hee Young</creator><creator>Park, Yujun</creator><creator>Nam, Soo Kyung</creator><creator>Lee, Kyu Sang</creator><creator>Oh, Heung‐Kwon</creator><creator>Kim, Duck‐Woo</creator><creator>Kang, Sung‐Bum</creator><creator>Kim, Woo Ho</creator><creator>Lee, Hye Seung</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>8FE</scope><scope>8FH</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>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1667-7986</orcidid></search><sort><creationdate>202101</creationdate><title>Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact</title><author>Na, Hee Young ; Park, Yujun ; Nam, Soo Kyung ; Lee, Kyu Sang ; Oh, Heung‐Kwon ; Kim, Duck‐Woo ; Kang, Sung‐Bum ; Kim, Woo Ho ; Lee, Hye Seung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4673-7ff560c6908bf0a547a8e4b7fa2a430c2e64d32dbebb57b3d99c6ad0cf6ccc673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antigens</topic><topic>Basic and Clinical Immunology</topic><topic>beta 2-Microglobulin - genetics</topic><topic>CD3 antigen</topic><topic>CD8 antigen</topic><topic>Chemotherapy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Down-Regulation - genetics</topic><topic>Female</topic><topic>Histocompatibility antigen HLA</topic><topic>Histocompatibility Antigens Class I - genetics</topic><topic>human leukocyte antigen class I</topic><topic>Humans</topic><topic>Immune checkpoint inhibitors</topic><topic>Immunohistochemistry</topic><topic>Immunohistochemistry - methods</topic><topic>Immunotherapy</topic><topic>Lung cancer</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Microsatellite Instability</topic><topic>Microsatellite Repeats - genetics</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Mutation</topic><topic>Original</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Statistical analysis</topic><topic>Tumors</topic><topic>Young Adult</topic><topic>β2‐microglobulin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Na, Hee Young</creatorcontrib><creatorcontrib>Park, Yujun</creatorcontrib><creatorcontrib>Nam, Soo Kyung</creatorcontrib><creatorcontrib>Lee, Kyu Sang</creatorcontrib><creatorcontrib>Oh, Heung‐Kwon</creatorcontrib><creatorcontrib>Kim, Duck‐Woo</creatorcontrib><creatorcontrib>Kang, Sung‐Bum</creatorcontrib><creatorcontrib>Kim, Woo Ho</creatorcontrib><creatorcontrib>Lee, Hye Seung</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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 science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Na, Hee Young</au><au>Park, Yujun</au><au>Nam, Soo Kyung</au><au>Lee, Kyu Sang</au><au>Oh, Heung‐Kwon</au><au>Kim, Duck‐Woo</au><au>Kang, Sung‐Bum</au><au>Kim, Woo Ho</au><au>Lee, Hye Seung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2021-01</date><risdate>2021</risdate><volume>112</volume><issue>1</issue><spage>91</spage><epage>100</epage><pages>91-100</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Downregulation of human leukocyte antigen (HLA) class I has been postulated to be a mechanism of adaptive immune escape in various tumors, especially microsatellite instability–high (MSI‐H) colorectal cancer (CRC). In this study, we aimed to investigate HLA class I and β2‐microglobulin (β2M) expression in MSI‐H and microsatellite‐stable (MSS) CRCs and determine its prognostic impact. The representative areas from the tumor center (TC) and tumor periphery (TP) from 300 CRCs, including 161 MSI‐H and 139 MSS cases, were selected to construct a tissue microarray. Immunohistochemistry (IHC) for HLA A/B/C, β2M, CD3, and CD8 was performed. Reduced HLA A/B/C expression was detected in 113 (70.2%) MSI‐H and 54 (38.8%) MSS cases, while reduced β2M expression was observed in 69 (42.9%) MSI‐H and 17 (12.2%) MSS cases. Although reduced β2M expression was associated with higher pathological tumor (pT) stage in MSI‐H CRC with borderline significance, no association was found between HLA A/B/C and β2M expression and survival. Interestingly, reduced HLA A/B/C expression in MSS was associated with higher stage, and reduced HLA A/B/C and β2M expression was an independent prognostic factor in multivariate analysis. In conclusion, reduced HLA A/B/C and β2M expression was frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitor. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor prognosis in MSS cancers. Overall, IHC for HLA A/B/C and β2M might be a feasible predictive or prognostic tool in CRC.
Reduced HLA A/B/C and β2M expression is frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitors. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor survival in MSS cancers, but not in MSI‐H tumors, indicating that cell‐mediated antitumoral immune response may also play an important role in MSS CRC. Together, IHC for HLA A/B/C and β2M can be a predictive or prognostic tool in CRC.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>33159376</pmid><doi>10.1111/cas.14723</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1667-7986</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over Antigens Basic and Clinical Immunology beta 2-Microglobulin - genetics CD3 antigen CD8 antigen Chemotherapy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Down-Regulation - genetics Female Histocompatibility antigen HLA Histocompatibility Antigens Class I - genetics human leukocyte antigen class I Humans Immune checkpoint inhibitors Immunohistochemistry Immunohistochemistry - methods Immunotherapy Lung cancer Lymphocytes Male Medical prognosis Medical research Microsatellite Instability Microsatellite Repeats - genetics Middle Aged Multivariate analysis Mutation Original Patients Prognosis Statistical analysis Tumors Young Adult β2‐microglobulin |
| title | Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact |
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