Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer
Abstract Downregulation of human leukocyte antigen (HLA) class I is one mechanism of escaping anti-tumor immunity by tumor cells. This study was conducted to compare HLA class I expression in ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC) and to evaluate its association with imm...
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| Format: | Article |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24890-3 |
| _version_ | 1811210814980358144 |
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| author | Song-Hee Han Milim Kim Yul Ri Chung Ji Won Woo Hye Yeon Choi So Yeon Park |
| author_facet | Song-Hee Han Milim Kim Yul Ri Chung Ji Won Woo Hye Yeon Choi So Yeon Park |
| author_sort | Song-Hee Han |
| collection | DOAJ |
| description | Abstract Downregulation of human leukocyte antigen (HLA) class I is one mechanism of escaping anti-tumor immunity by tumor cells. This study was conducted to compare HLA class I expression in ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC) and to evaluate its association with immune cell infiltration of the tumors and clinical outcome of the patients. A total of 830 cases comprising 288 DCIS and 542 IBC were included in this study. Immunohistochemistry for HLA class I expression was performed using HLA-ABC in tissue microarrays and was analyzed in relation to clinicopathologic characteristics of tumors and infiltration of CD4+, CD8+, and FOXP3+ tumor-infiltrating lymphocyte (TIL) subsets and PD-L1+ immune cells. As a whole, there was no difference in HLA class I expression between DCIS and IBC when dichotomized into high or low expression. However, in the HR-negative group, a high level of HLA class I expression was more frequent in IBC than DCIS. On the contrary, in the HR-positive group, a complete loss of HLA class I expression was more frequently observed in IBC than DCIS. High HLA class I expression level was generally associated with aggressive clinicopathologic features of IBC and was associated with high CD4+, CD8+, and FOXP3+ TIL and PD-L1+ immune cell infiltration in both DCIS and IBC. In survival analyses, HLA class I expression was not associated with clinical outcome in DCIS and IBC as a whole; however, low HLA class I expression was associated with poor clinical outcome in HR-negative IBC, especially in triple-negative subtype. In conclusion, this study showed that HLA class I expression increased in association with increased immune cell infiltration during in situ to invasive transition of HR-negative breast cancer, and HLA class I down-regulation had a prognostic value in HR-negative breast cancer. |
| first_indexed | 2024-04-12T05:02:14Z |
| format | Article |
| id | doaj.art-1ebc1a5be08b44028b49bc2ad021eac1 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T05:02:14Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1ebc1a5be08b44028b49bc2ad021eac12022-12-22T03:46:58ZengNature PortfolioScientific Reports2045-23222022-11-0112111110.1038/s41598-022-24890-3Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancerSong-Hee Han0Milim Kim1Yul Ri Chung2Ji Won Woo3Hye Yeon Choi4So Yeon Park5Department of Pathology, Seoul National University College of MedicineDepartment of Pathology, Seoul National University College of MedicinePathology Center, Seegene Medical FoundationDepartment of Pathology, Seoul National University College of MedicineDepartment of Pathology, Seoul National University Bundang HospitalDepartment of Pathology, Seoul National University College of MedicineAbstract Downregulation of human leukocyte antigen (HLA) class I is one mechanism of escaping anti-tumor immunity by tumor cells. This study was conducted to compare HLA class I expression in ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC) and to evaluate its association with immune cell infiltration of the tumors and clinical outcome of the patients. A total of 830 cases comprising 288 DCIS and 542 IBC were included in this study. Immunohistochemistry for HLA class I expression was performed using HLA-ABC in tissue microarrays and was analyzed in relation to clinicopathologic characteristics of tumors and infiltration of CD4+, CD8+, and FOXP3+ tumor-infiltrating lymphocyte (TIL) subsets and PD-L1+ immune cells. As a whole, there was no difference in HLA class I expression between DCIS and IBC when dichotomized into high or low expression. However, in the HR-negative group, a high level of HLA class I expression was more frequent in IBC than DCIS. On the contrary, in the HR-positive group, a complete loss of HLA class I expression was more frequently observed in IBC than DCIS. High HLA class I expression level was generally associated with aggressive clinicopathologic features of IBC and was associated with high CD4+, CD8+, and FOXP3+ TIL and PD-L1+ immune cell infiltration in both DCIS and IBC. In survival analyses, HLA class I expression was not associated with clinical outcome in DCIS and IBC as a whole; however, low HLA class I expression was associated with poor clinical outcome in HR-negative IBC, especially in triple-negative subtype. In conclusion, this study showed that HLA class I expression increased in association with increased immune cell infiltration during in situ to invasive transition of HR-negative breast cancer, and HLA class I down-regulation had a prognostic value in HR-negative breast cancer.https://doi.org/10.1038/s41598-022-24890-3 |
| spellingShingle | Song-Hee Han Milim Kim Yul Ri Chung Ji Won Woo Hye Yeon Choi So Yeon Park Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer Scientific Reports |
| title | Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer |
| title_full | Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer |
| title_fullStr | Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer |
| title_full_unstemmed | Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer |
| title_short | Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer |
| title_sort | expression of hla class i is associated with immune cell infiltration and patient outcome in breast cancer |
| url | https://doi.org/10.1038/s41598-022-24890-3 |
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