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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780028/ https://www.ncbi.nlm.nih.gov/pubmed/33159376 http://dx.doi.org/10.1111/cas.14723 |
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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_facet | 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 | Na, Hee Young |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7780028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77800282021-01-08 Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact 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 Cancer Sci Basic and Clinical Immunology 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. John Wiley and Sons Inc. 2020-11-28 2021-01 /pmc/articles/PMC7780028/ /pubmed/33159376 http://dx.doi.org/10.1111/cas.14723 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Basic and Clinical Immunology 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 Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact |
title | Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact |
title_full | Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact |
title_fullStr | Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact |
title_full_unstemmed | Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact |
title_short | Expression of human leukocyte antigen class I and β2‐microglobulin in colorectal cancer and its prognostic impact |
title_sort | expression of human leukocyte antigen class i and β2‐microglobulin in colorectal cancer and its prognostic impact |
topic | Basic and Clinical Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780028/ https://www.ncbi.nlm.nih.gov/pubmed/33159376 http://dx.doi.org/10.1111/cas.14723 |
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