PD-L1 Expression in Receptor-Negative Breast Cancer Tissue
DOI:
https://doi.org/10.15407/exp-oncology.2024.04.324Keywords:
steroid hormone receptors, breast cancer, PD-L1Abstract
Background. The high heterogeneity and pathogenetic diversity of breast cancer (BCa) indicate the need for further study of tumor cell biology in order to identify molecular biological markers associated with the aggressiveness of tumors with a negative receptor status. Among many factors that may be involved in the initiation and progression of this form of cancer, the study of the immune components of tumor microenvironment, in particular PD-L1, is considered promising. Aim. To investigate the relationship between PD-L1 expression in tumor tissue and clinical and pathological characteristics of BCa, taking into account the status of steroid hormone receptors. Materials and Methods. In tumor tissue of 116 patients with stage I—II BCa, the mRNA levels of CD274 gene were determined using the real-time quantitative polymerase chain reaction. The expression of PD-L1 was studied by the immunohistochemical method. Results. The tissue of receptor-negative BCa was characterized by a significant decrease in the CD274 mRNA level against the background of the increased PD-L1 expression compared to neoplasms positive for the expression of steroid hormone receptors. An inverse correlation was found between PD-L1 at the protein level and the age of patients with receptor-negative BCa (r = –0.613, p = 0.00003). We showed that a characteristic feature of receptor-negative BCa in menopausal patients is the increased expression of PD-L1 both at the protein and mRNA levels (p = 0.005 and p = 0.046, respectively). The correlation of PD-L1 expression with metastatic lesions in regional lymph nodes (p = 0.050), tumor differentiation grade (p = 0.001), and the patient survival rate was revealed. Conclusions. The obtained data indicated the expediency of using PD-L1 expression indicators for in-depth characterization of the tumor microenvironment of receptor-negative BCa, which will allow for the personalized correction of therapy regimens contributing to the improvement of the patients' quality of life.
References
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. https://doi.org/10.3322/caac.21660
Guo L, Kong D, Liu J, et al. Breast cancer heterogeneity and its implication in personalized precision therapy [pub- lished correction appears in Exp Hematol Oncol. 2024;13(1):7. doi: 10.1186/s40164-024-00472-z]. Exp Hematol On- col. 2023;12(1):3. https://doi.org/10.1186/s40164-022-00363-1
Yang T, Li W, Huang T, Zhou J. Immunotherapy targeting PD-1/PD-L1 in early-stage triple-negative breast cancer.
J Pers Med. 2023;13(3):526. https://doi.org/10.3390/jpm13030526
Li J, Wu J, Han J. Analysis of tumor microenvironment heterogeneity among breast cancer subtypes to identify subtype-specific signatures. Genes (Basel). 2022;14(1):44. https://doi.org/10.3390/genes14010044
Zhu Y, Zhu X, Tang C, et al. Progress and challenges of immunotherapy in triple-negative breast cancer. Biochim Biophys Acta Rev Cancer. 2021;1876(2):188593. https://doi.org/10.1016/j.bbcan.2021.188593
Shuai C, Yang X, Pan H, Han W. Estrogen receptor downregulates expression of PD-1/PD-L1 and infiltration of CD8+ T cells by inhibiting IL-17 signaling transduction in breast cancer. Front Oncol. 2020;10:582863. https://doi. org/10.3389/fonc.2020.582863
Werner LR, Gibson KA, Goodman ML, et al. Progesterone promotes immunomodulation and tumor development in the murine mammary gland. J Immunother Cancer. 2021;9(5):e001710. https://doi.org/10.1136/jitc-2020-001710
Bastaki S, Irandoust M, Ahmadi A, et al. PD-L1/PD-1 axis as a potent therapeutic target in breast cancer. Life Sci. 2020;247:117437. https://doi.org/10.1016/j.lfs.2020.117437
Chekhun V, Borikun T, Zadvornyi T, et al. Osteonectin (SPARC) prognostic value in prostate cancer. Pathol Res Pract. 2024;254:155053. https://doi.org/10.1016/j.prp.2023.155053
Zhang JD, Ruschhaupt M, Biczok R. ddCt method for qRT–PCR data analysis. Available from: https://www.biocon- ductor.org/packages/devel/bioc/vignettes/ddCt/inst/doc/rtPCR.pdf Accessed October 29, 2024.
McClelland RA, Wilson D, Leake R, et al. A multicentre study into the reliability of steroid receptor immunocy- tochemical assay quantification. British Quality Control Group. Eur J Cancer. 1991;27(6):711-715. https://doi. org/10.1016/0277-5379(91)90171-9
Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue - a review. Diagn Pathol. 2014;9:221. https://doi.org/10.1186/s13000-014-0221-9
Qin T, Zeng YD, Qin G, et al. High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer. Oncotarget. 2015;6(32):33972-33981. https://doi.org/10.18632/oncotarget.5583
Antony GR, Augustine P, Parambil ST, et al. Immunohistochemical expression of PD-L1 and MDR1 in breast tu- mors: association with clinico-pathological parameters and treatment outcome. Clin Exp Med. 2023;23(3):859-869. https://doi.org/10.1007/s10238-022-00852-x
Alkaabi D, Arafat K, Sulaiman S, et al. PD-1 Independent role of PD-L1 in triple-negative breast cancer progression.
Int J Mol Sci. 2023;24(7):6420. https://doi.org/10.3390/ijms24076420
Yi M, Niu M, Xu L, et al. Regulation of PD-L1 expression in the tumor microenvironment. J Hematol Oncol. 2021;14(1):10. https://doi.org/10.1186/s13045-020-01027-5
Feng C, Zhang L, Chang X, et al. Regulation of post-translational modification of PD-L1 and advances in tumor im- munotherapy. Front Immunol. 2023;14:1230135. https://doi.org/10.3389/fimmu.2023.1230135
Kiriyama Y, Nochi H. Regulation of PD-L1 expression by nuclear receptors. Int J Mol Sci. 2023;24(12):9891. https:// doi.org/10.3390/ijms24129891
Chekhun V, Martynyuk О, Lukianova Y, et al. Features of breast cancer in patients of young age: search for diagno- sis optimization and personalized treatment. Exp Oncol. 2023;45(2):139-150. https://doi.org/10.15407/exp-oncolo- gy.2023.02.139
Chekhun V, Mushii O, Zadvornyi T, et al. Features of col1a1 expression in breast cancer tissue of young patients.
Exp Oncol. 2023;45(3):351-363. https://doi.org/10.15407/exp-oncology.2023.03.351
Lukianova N, Mushii O, Borikun T, et al. Pattern of mmp2 and mmp9 expression depends on breast cancer patients' age. Exp Oncol. 2023;45(1):17-27. https://doi.org/10.15407/exp-oncology.2023.01.017
Erraez-Jaramillo PJ, Aguirre-Flores E, Athie-Meza LF, et al. Expression of programmed death ligand 1 in breast can- cer in Mexican women. World J Oncol. 2022;13(4):185-189. https://doi.org/10.14740/wjon1512
Cirqueira MB, Mendonça CR, Noll M, et al. Prognostic role of PD-L1 expression in invasive breast cancer: A system- atic review and meta-analysis. Cancers (Basel). 2021;13(23):6090. https://doi.org/10.3390/cancers13236090
AiErken N, Shi HJ, Zhou Y, et al. High PD-L1 expression is closely associated with tumor-infiltrating lymphocytes and leads to good clinical outcomes in chinese triple negative breast cancer patients. Int J Biol Sci. 2017;13(9):1172- 1179. https://doi.org/10.7150/ijbs.20868
Chen L, Huang S, Liu Q, et al. PD-L1 protein expression is associated with good clinical outcomes and nomogram for prediction of disease-free survival and overall survival in breast cancer patients received neoadjuvant chemo- therapy. Front Immunol. 2022;13:849468. https://doi.org/10.3389/fimmu.2022.849468
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
