STAT3 and PD-L1 are negatively correlated with ATM and have impact on the prognosis of triple-negative breast cancer patients with low ATM expression
Introduction Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). Materials and methods We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. Results We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. Conclusion Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors..
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:196 |
|---|---|
| Enthalten in: |
Breast cancer research and treatment - 196(2022), 1 vom: 03. Sept., Seite 45-56 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Song, Yuan-Ming [VerfasserIn] |
|---|
| Links: |
Volltext [lizenzpflichtig] |
|---|
| BKL: | |
|---|---|
| Themen: |
P-c-src Y419 |
| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
|---|
| doi: |
10.1007/s10549-022-06679-0 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
OLC2079703005 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | OLC2079703005 | ||
| 003 | DE-627 | ||
| 005 | 20230516084249.0 | ||
| 007 | tu | ||
| 008 | 221221s2022 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s10549-022-06679-0 |2 doi | |
| 035 | |a (DE-627)OLC2079703005 | ||
| 035 | |a (DE-He213)s10549-022-06679-0-p | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q VZ |
| 084 | |a 44.00 |2 bkl | ||
| 100 | 1 | |a Song, Yuan-Ming |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a STAT3 and PD-L1 are negatively correlated with ATM and have impact on the prognosis of triple-negative breast cancer patients with low ATM expression |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. | ||
| 520 | |a Introduction Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). Materials and methods We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. Results We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. Conclusion Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors. | ||
| 650 | 4 | |a Triple-negative breast cancer (TNBC) | |
| 650 | 4 | |a The ataxia-telangiectasia mutation gene (ATM) | |
| 650 | 4 | |a Programmed cell death ligand-1 (PD-L1) | |
| 650 | 4 | |a STAT3 | |
| 650 | 4 | |a p-c-src Y419 | |
| 700 | 1 | |a Qian, Xiao-Long |4 aut | |
| 700 | 1 | |a Xia, Xiao-Qing |4 aut | |
| 700 | 1 | |a Li, Ya-Qing |4 aut | |
| 700 | 1 | |a Sun, Yuan-Yuan |4 aut | |
| 700 | 1 | |a Jia, Yu-Mian |4 aut | |
| 700 | 1 | |a Wang, Jin |4 aut | |
| 700 | 1 | |a Xue, Hui-Qin |4 aut | |
| 700 | 1 | |a Gao, Guang-Shen |4 aut | |
| 700 | 1 | |a Wang, Xiao-Zi |4 aut | |
| 700 | 1 | |a Zhang, Xin-Min |4 aut | |
| 700 | 1 | |a Guo, Xiao-Jing |0 (orcid)0000-0003-3753-2900 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Breast cancer research and treatment |d Springer US, 1981 |g 196(2022), 1 vom: 03. Sept., Seite 45-56 |w (DE-627)167913557 |w (DE-600)604563-7 |w (DE-576)01590217X |x 0167-6806 |7 nnns |
| 773 | 1 | 8 | |g volume:196 |g year:2022 |g number:1 |g day:03 |g month:09 |g pages:45-56 |
| 856 | 4 | 1 | |u https://doi.org/10.1007/s10549-022-06679-0 |z lizenzpflichtig |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OLC-DE-84 | ||
| 936 | b | k | |a 44.00 |q VZ |
| 951 | |a AR | ||
| 952 | |d 196 |j 2022 |e 1 |b 03 |c 09 |h 45-56 | ||