Peripheral blood CD8+-lymphocytes populations and its value for direct and outlying treatment results in triple negative breast cancer patients

• Tatiana N. Zabotina
• Antonina I. Chertkova
• Zaira G. Kadagidze
• Anna A. Borunova
• Esma K. Shoua
• Olga O. Gordeeva
• Andrey A. Meshcheryakov

Abstract

Introduction. Triple negative breast cancer (TN BC) is characterized by an aggressive course and a high likelihood of the disease recurrence. An important role in the regulation of the growth of malignant neoplasms, as well as in the effectiveness of various types of antitumor therapy, is played by the immune system. Establishing the relationship of some CD8-positive lymphocyte populations with the effectiveness of treating patients with breast cancer may help establish reliable immunological predictive and prognostic factors and increase the effectiveness of treatment for patients.

The aim of the study was to determine the value of the original number of CD8⁺ peripheral blood lymphocytes (CD8⁺, CD3⁺CD8⁺, CD8⁺CD28⁺, CD8⁺CD28^–, CD3^–CD8⁺) cells for immediate (degree of therapeutic tumor pathomorphosis) and distant (progression of disease and survival) of treatment results of patients with three-year negative breast cancer.

Material and methods. In patients with II–III stages of TN BC (n = 72, age median 50 years) before the start of neoadjuvant chemotherapy (NACT) (cisplatin + paclitaxel), the percentage of peripheral blood CD8⁺, CD3⁺CD8⁺, CD8⁺CD28⁺, CD8⁺CD28⁻, CD3⁻CD8⁺ lymphocytes was determined using a multi-parameter cytometric analysis. The relationship of the initial number of these cell populations with the degree of therapeutic pathomorphosis (TP), disease progression, and patient survival was studied. The observation period was 60 months.

Results. In patients with TP grade 4, in patients without disease progression and surviving patients, the percentage of CD8⁺CD28⁺-lymphocytes and the ratio of CD8⁺CD28/CD8⁺CD28⁻ were statistically significantly higher before treatment than in patients with TP grade 1–3, recurrent patients and deceased patients. An increase of the initial number of CD8⁺CD28⁺-lymphocytes and the СD8⁺CD28/CD8⁺CD28⁻ ratio was associated with an increase in relapse-free (RFS) and overall survival (OS) of patients compared with patients in whom these showings were reduced. In patients who died during the observation period, the number of CD3⁻CD8⁺-lymphocytes was increased prior to chemotherapy. An increase in the number of these cells was also associated with a decrease in OS.

Conclusion. Populations of CD8⁺CD28⁺ peripheral blood lymphocytes and the ratio of CD8⁺CD28/CD8⁺CD28⁻ cells could be possible predictive factors for patients with II–III stages of TNBC receiving NACT (cisplatin and paclitaxel).

Keywords:TN breast cancer; CD8+-lymphocyte populations; neoadjuvant chemotherapy; degree of therapeutic pathomorphosis; relapse-free survival; overall survival

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