Neoadjuvant chemotherapy modulates exhaustion of T cells in breast cancer patients

PLoS One. 2023 Feb 10;18(2):e0280851. doi: 10.1371/journal.pone.0280851. eCollection 2023.

Abstract

Breast cancer is the leading cause of cancer deaths in women worldwide. It has been observed that the incidence of breast cancer increases linearly with age after 45, which suggest a link between cancer, aging, and senescence. A growing body of evidence indicates that the immunosuppressive tumor network in breast cancer patients can lead to T-cell exhaustion and senescence. Cytotoxic chemotherapy is a common treatment for many cancers, and it is hypothesized that its efficacy may be related to immune activation. However, the effects of neoadjuvant chemotherapy on T-cell dysfunction in breast cancer patients are not fully understood. This study aimed to evaluate the impact of neoadjuvant chemotherapy on the expression of exhaustion and senescence markers in T cells in women with breast cancer. Our results showed that T cells from breast cancer patients have a reduced ability to respond to stimulation in-vitro and an increased expression of senescence and exhaustion-associated markers, such as TIM-3, LAG3, and CD57. Furthermore, we found that neoadjuvant chemotherapy has an immunomodulatory effect and reduces the expression of exhaustion markers. Our observations of the immune phenotype of T cells during neoadjuvant chemotherapy treatment highlight its ability to stimulate the immune system against cancer. Therefore, monitoring the response of T cells during chemotherapy may enable early prediction of clinical response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Humans
  • Neoadjuvant Therapy
  • Neoplasms*
  • Phenotype
  • T-Lymphocytes*

Grants and funding

División de Investigación Sede Bogotá, Vicedecanatura de Investigación y Extensión_Facultad de Medicina, Universidad Nacional de Colombia (Códigos Hermes: 47334, 48357, 46309, 44596, 38571, 50297, 57872). MinCiencias (Contrato No. 903 de 2019, Contrato No. 844 de 2017, Contrato No. 772 de 2018, Contrato No. 847 de 2020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.