Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy
Abstract Neoadjuvant therapy (NAT) treats early‐stage breast cancers, especially triple‐negative breast cancers (TNBCs). NAT improves pathological complete response (pCR) rates for different breast cancer patients. Recently, immune checkpoint inhibitors that target programmed death 1 (PD‐1) or progr...
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| Format: | Article |
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Wiley
2023-02-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.5207 |
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| author | Mengxue Han Jinze Li Si Wu Chun Wu Yongqiang Yu Yueping Liu |
| author_facet | Mengxue Han Jinze Li Si Wu Chun Wu Yongqiang Yu Yueping Liu |
| author_sort | Mengxue Han |
| collection | DOAJ |
| description | Abstract Neoadjuvant therapy (NAT) treats early‐stage breast cancers, especially triple‐negative breast cancers (TNBCs). NAT improves pathological complete response (pCR) rates for different breast cancer patients. Recently, immune checkpoint inhibitors that target programmed death 1 (PD‐1) or programmed death ligand 1 (PD‐L1) in combination with NAT have shown antitumor activity in patients with early breast cancer. However, the tumor immune microenvironment (TME) in different subtypes of breast cancers, like TNBC, hormone receptor‐positive (HR+), and human epidermal growth factor receptor 2 amplified (HER2+) and its changes by NAT remain to be fully characterized. We analyzed pre‐NAT tumor biopsies from TNBC (n = 27), HR+ (n = 24), and HER2+ (n = 30) breast cancer patients who received NAT, followed by surgery. The different immune makers (PD‐1, PD‐L1, CD3, and CD8) of tumor‐infiltrating lymphocytes (TILs) were identified with immunofluorescence‐based microenvironment analysis. TILs within cancer parenchyma (iTILs) and in cancer stroma (sTILs) were counted separately. We found that PD‐L1+ cells in tumor and stroma were significantly higher in TNBC patients than in others. PD‐L1+ sTILs were significantly higher in pCR than in non‐pCR patients of all the subtypes. The infiltration scores of B‐cell memory, T‐cell CD4+ memory activated, T‐cell follicular helper, and Macrophage M0 and M1 were relatively higher in TNBC patients, indicating immunoreactive TME in TNBC. Analysis of TCGA‐BRCA RNA‐seq indicated that PD‐L1 was highly expressed in TNBC patients compared with HR+ and HER2+ patients. Higher PD‐L1 expression in TNBC patients was associated with significantly longer overall survival (OS). Our results demonstrated that PD‐L1 expression level of iTILs and sTILs is highest in TNBC among breast cancers. TNBC patients had significantly different immunoreactive TME compared with HR+ and HER2+ patients, suggesting potentially favorable outcomes for immunotherapy in these patients. Also, PD‐L1+ could be a powerful predictor of pCR in TNBC patients after NAT. |
| format | Article |
| id | doaj-art-b6e72c570e9c45ec9249bd35fb52f584 |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-b6e72c570e9c45ec9249bd35fb52f5842025-08-20T02:23:32ZengWileyCancer Medicine2045-76342023-02-011232906291710.1002/cam4.5207Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapyMengxue Han0Jinze Li1Si Wu2Chun Wu3Yongqiang Yu4Yueping Liu5Department of Pathology The Fourth Hospital of Hebei Medical University Shijiazhuang ChinaDepartment of Pathology The Fourth Hospital of Hebei Medical University Shijiazhuang ChinaDepartment of Pathology The Fourth Hospital of Hebei Medical University Shijiazhuang ChinaDepartment of Pathology The Fourth Hospital of Hebei Medical University Shijiazhuang ChinaDepartment of Pathology The Fourth Hospital of Hebei Medical University Shijiazhuang ChinaDepartment of Pathology The Fourth Hospital of Hebei Medical University Shijiazhuang ChinaAbstract Neoadjuvant therapy (NAT) treats early‐stage breast cancers, especially triple‐negative breast cancers (TNBCs). NAT improves pathological complete response (pCR) rates for different breast cancer patients. Recently, immune checkpoint inhibitors that target programmed death 1 (PD‐1) or programmed death ligand 1 (PD‐L1) in combination with NAT have shown antitumor activity in patients with early breast cancer. However, the tumor immune microenvironment (TME) in different subtypes of breast cancers, like TNBC, hormone receptor‐positive (HR+), and human epidermal growth factor receptor 2 amplified (HER2+) and its changes by NAT remain to be fully characterized. We analyzed pre‐NAT tumor biopsies from TNBC (n = 27), HR+ (n = 24), and HER2+ (n = 30) breast cancer patients who received NAT, followed by surgery. The different immune makers (PD‐1, PD‐L1, CD3, and CD8) of tumor‐infiltrating lymphocytes (TILs) were identified with immunofluorescence‐based microenvironment analysis. TILs within cancer parenchyma (iTILs) and in cancer stroma (sTILs) were counted separately. We found that PD‐L1+ cells in tumor and stroma were significantly higher in TNBC patients than in others. PD‐L1+ sTILs were significantly higher in pCR than in non‐pCR patients of all the subtypes. The infiltration scores of B‐cell memory, T‐cell CD4+ memory activated, T‐cell follicular helper, and Macrophage M0 and M1 were relatively higher in TNBC patients, indicating immunoreactive TME in TNBC. Analysis of TCGA‐BRCA RNA‐seq indicated that PD‐L1 was highly expressed in TNBC patients compared with HR+ and HER2+ patients. Higher PD‐L1 expression in TNBC patients was associated with significantly longer overall survival (OS). Our results demonstrated that PD‐L1 expression level of iTILs and sTILs is highest in TNBC among breast cancers. TNBC patients had significantly different immunoreactive TME compared with HR+ and HER2+ patients, suggesting potentially favorable outcomes for immunotherapy in these patients. Also, PD‐L1+ could be a powerful predictor of pCR in TNBC patients after NAT.https://doi.org/10.1002/cam4.5207immune microenvironmentneoadjuvant therapyPD‐L1triple‐negative breast cancertumor‐infiltrating lymphocytes |
| spellingShingle | Mengxue Han Jinze Li Si Wu Chun Wu Yongqiang Yu Yueping Liu Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy Cancer Medicine immune microenvironment neoadjuvant therapy PD‐L1 triple‐negative breast cancer tumor‐infiltrating lymphocytes |
| title | Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy |
| title_full | Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy |
| title_fullStr | Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy |
| title_full_unstemmed | Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy |
| title_short | Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy |
| title_sort | comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy |
| topic | immune microenvironment neoadjuvant therapy PD‐L1 triple‐negative breast cancer tumor‐infiltrating lymphocytes |
| url | https://doi.org/10.1002/cam4.5207 |
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