PMID- 36437379 OWN - NLM STAT- MEDLINE DCOM- 20221129 LR - 20230113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 12 IP - 1 DP - 2022 Nov 27 TI - Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer. PG - 20367 LID - 10.1038/s41598-022-24890-3 [doi] LID - 20367 AB - 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. CI - (c) 2022. The Author(s). FAU - Han, Song-Hee AU - Han SH AD - Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Department of Pathology, Dong-A University College of Medicine, Busan, Republic of Korea. FAU - Kim, Milim AU - Kim M AD - Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Department of Pathology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi, 13620, Republic of Korea. FAU - Chung, Yul Ri AU - Chung YR AD - Pathology Center, Seegene Medical Foundation, Seoul, Republic of Korea. FAU - Woo, Ji Won AU - Woo JW AD - Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea. AD - Department of Pathology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi, 13620, Republic of Korea. FAU - Choi, Hye Yeon AU - Choi HY AD - Department of Pathology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi, 13620, Republic of Korea. FAU - Park, So Yeon AU - Park SY AD - Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea. sypmd@snu.ac.kr. AD - Department of Pathology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi, 13620, Republic of Korea. sypmd@snu.ac.kr. LA - eng GR - 02-2020-0043/Seoul National University Bundang Hospital/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221127 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (B7-H1 Antigen) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Forkhead Transcription Factors) SB - IM MH - Humans MH - *Carcinoma, Intraductal, Noninfiltrating/pathology MH - B7-H1 Antigen/metabolism MH - *Triple Negative Breast Neoplasms/metabolism MH - Lymphocytes, Tumor-Infiltrating MH - Histocompatibility Antigens Class I/metabolism MH - Forkhead Transcription Factors/metabolism PMC - PMC9701770 COIS- The authors declare no competing interests. EDAT- 2022/11/28 06:00 MHDA- 2022/11/30 06:00 PMCR- 2022/11/27 CRDT- 2022/11/27 23:26 PHST- 2022/05/03 00:00 [received] PHST- 2022/11/22 00:00 [accepted] PHST- 2022/11/27 23:26 [entrez] PHST- 2022/11/28 06:00 [pubmed] PHST- 2022/11/30 06:00 [medline] PHST- 2022/11/27 00:00 [pmc-release] AID - 10.1038/s41598-022-24890-3 [pii] AID - 24890 [pii] AID - 10.1038/s41598-022-24890-3 [doi] PST - epublish SO - Sci Rep. 2022 Nov 27;12(1):20367. doi: 10.1038/s41598-022-24890-3.