Prognostic and Predictive Capabilities of Tumor-Infiltrating Lymphocytes in Breast Cancer

The aim of the study is to evaluate the prognostic and predictive capabilities of tumorinfiltrating lymphocytes in breast cancer (BC); to study the prognostic value of T-cell (CD8+, CD3+) lymphocyte infiltration of the tumor and the level of T-regulatory (CD4+) lymphocytes; to study the prognostic and predictive value of the expression of proteins Forkhead Box Protein 3, check-point PD-1, PDL1. Materials and methods. The content of tumor-infiltrating lymphocytes and their quantitative ratio and correlation with regulatory genes were assessed. Archival material was used in the work. The study included archival data from the cancer registry of 1240 patients treated at the N.N. Petrov Cancer Research Institute from 2000 to 2009. Histological preparations stained with hematoxylin and eosin were scanned. Ten-year relapse-free and overall survival were assessed. Results. About 80% of patients with BC have low levels of tumor infiltration by CD8+ cytotoxic T lymphocytes and CD3+ lymphocytes. Expression of the PD-L1 gene was detected more often (29.5%) in triple-negative breast cancer, 1.5 times less often (18.2%) in HER2+ BC and extremely rarely (1.5%) in luminal A subtype. Severe (more than 10%) lymphocytic infiltration of CD8+ and CD3+ with low expression of PD-L1 and FOXP3 improves relapse-free and overall survival of patients with BC. Conclusion. The inclusion of lymphocytic infiltration of the tumor as a prognostic biomarker represents an important step in understanding the biology of BC.

1. Semiglazov V.F., Krivorot'ko P.V., Semiglazov V.V. Immunologiya raka molochnoi zhelezy. Moscow: SIMK; 2019 (In Russ.).

2. Semiglazov V.F., Tseluyko A.I., Donskikh R.V., Smirnova V.O., Artemyeva A.S., Krivorotko P.V. Immunology and Immunotherapy of Breast Cancer. Effective Pharmacotherapy. 2020;16(11):46–51 (In Russ.).

3. Semiglazov V.V., Krivorot'ko P.V., Semiglazov V.F., Donskikh R.V., Paltuev R.M. Mezhdunarodnye rekomendatsii po lecheniyu rannego raka molochnoi zhelezy. Moscow: MK; 2020 (In Russ.).

4. Tseluiko A.I., Semiglazov V.F., Kudaybergenova A.G., Artemyeva A.S., Smirnova V.O., Apollonova V.S., Donskikh R.V. Some Aspects of Antitumor Immunity in Breast Cancer. Effective Pharmacotherapy. 2021;17(2):20–7. doi: 10.33978/2307-3586-2021-17-2-6-14

5. Denkert C., Loibl S., Noske A., Roller M., Müller B.M., Komor M., et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2010 Jan 1;28(1):105–13. doi: 10.1200/JCO.2009.23.7370

6. Denkert C., von Minckwitz G., Brase J.C., Sinn B.V., et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015 Mar 20;33(9):983-91. doi: 10.1200/JCO.2014.58.1967

7. Miyashita M., Sasano H., Tamaki K., Hirakawa H., Takahashi Y., Nakagawa S., et al. Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study. Breast cancer research: BCR [Internet]. 2015 Sep 4;17(1):124. doi: 10.1186/s13058-015-0632-x