Original Article

Evaluation of the Role of Tumor-Infiltrating Lymphocytes and CD8+ Cytotoxic Lymphocytes in the Survival of Patients with Breast Cancer


Background: This study aimed to evaluate the significance of tumor lymphocyte infiltration (TIL) and the number of CD8+ T cells in breast cancer and their relationship with the other clinicopathological factors and overall survival (OS) was investigated.

Materials and Methods: The studied samples were breast cancer patients (2005-2017) referring to the medical oncology departments for treatment. Pathologic samples of breast cancer patients were evaluated in terms of TIL and positive immunohistochemical staining for CD8 cytotoxic cells.

Results: 299 patients were entered into the study, 3 male and 296 female. Their mean follow-up period was 61 months. Statistical findings indicated that lymph involvement is more accompanied by low TIL within the tumor (0.011). Correlations were observed between the estrogen, progesterone receptors, P53 state, and TIL; which were significant by P-value<0.049, P-value=0.024, P-value =0.002, respectively. With any Ki67 value, the number of patients with less than 30% TIL was more considerable than the two other groups with lymphocyte cut-off of 30-50% and more than 50%. Comparison of the OS of patients with positive and negative CD8 cytotoxic lymphocytes in 45 patients with lymphocyte infiltration of equal or more than 40% showed that the OS results were in favor of patients with CD8+ cytotoxic lymphocyte (0.022). Out of 299 patients, 17 died.

Conclusion: Our findings showed that in cases of CD8+ cytotoxic lymphocytes in tumors, the OS of the patients will be enhanced which can act as an independent.


1. Stanton SE, Adams S, Disis ML. Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: a systematic review. JAMA Oncol. 2016; 2 (10): 1354-1360.
2. Shuzhen Liu, Jonathan Lachapelle, Samuel Leung, et al. CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer. Breast Cancer Res. 2012; 14(2): R48.
3. Bhat P, Leggatt G, Waterhouse N, et al. Interferon-γ derived from cytotoxic lymphocytes directly enhances their motility and cytotoxicity. Cell Death Dis.2017;8(6):e2836.
4. Solinas C, Gombos A, Latifyan S, et al. Targeting immune checkpoints in breast cancer: an update of early results. ESMO Open 2017;2(5):e000255.
5. Krasniqi E, Barchiesi, G, Pizzuti L, et al. Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives. J Hematol Oncol. 2019; 12(1): 111
6. Rahir G, Wathelet N, Hanoteau A, et al. Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H-2Kd-specific CD8+ T cells. Int J Cancer. 2014;134(12):2841–52.
7. Lorenzo Galluzzi, Aitziber Buque ́, Oliver Kepp, et al. Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. Cancer Cell. 2015; 28(6):690-714.
8. Blows FM, Driver KE, Schmidt MK, et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med. 2010; 7(5):e1000279.
9. Dobrzanski MJ. Expanding roles for CD4 T cells and their subpopulations in tumor immunity and therapy. Front Oncol. 2013;3:63.
10. Miyoshi Y, Shien T, Ogiya A, et al.(2019). Associations in tumor infiltrating lymphocytes between clinicopathological factors and clinical outcomes in estrogen receptor positive/human epidermal growth factor receptor type 2 negative breast cancer. Oncol Lett. 2019;17(2): 2177-2186.
11. García-Teijido P, Pelaez-Fernández I, Fernández-Pérez Y, et al.Tumor-infiltrating lymphocytes in triple negative breast cancer: the future of immune targeting. Clin Med Insights Oncol.2016; 10(Suppl 1): 31-9.
12. Kurozumi S, Matsumoto H, Kurosumi M, et al. Prognostic significance of tumour infiltrating lymphocytes for oestrogen receptor negative breast cancer without lymph node metastasis. Oncol Lett. 2019;17(3):2647-2656.
13. Vihervuori H, Autere TA, Repo H. et al. Tumor-infiltrating lymphocytes and CD8+ T cells predict survival of triple-negative breast cancer. J Cancer Res Clin Oncol. 2019; 145(12):3105-3114.
14. Kim I, Sanchez K, McArthur HL, et al. Immunotherapy in Triple-Negative Breast Cancer: Present and Future. Curr Breast Cancer Rep. 2019; 11: 259-271.
IssueVol 17, No 1 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijhoscr.v17i1.11708
Breast cancer; CD8 cytotoxic lymphocytes; Overall Survival; Tumor-infiltrating lymphocytes

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Shojaei S, Aznab M, Rahimi A, Ahmadi SM, Eslampia K, Golpazir A, Iravani M. Evaluation of the Role of Tumor-Infiltrating Lymphocytes and CD8+ Cytotoxic Lymphocytes in the Survival of Patients with Breast Cancer. Int J Hematol Oncol Stem Cell Res. 2023;17(1):9-17.