Monitoring the responsiveness of T and antigen presenting cell compartments in breast cancer patients is useful to predict clinical tumor response to neoadjuvant chemotherapy

David A. Bernal-Estévez, Oscar García, Ramiro Sánchez, Carlos A. Parra-López

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: Vaccination of mice with tumors treated with Doxorubicin promotes a T cell immunity that relies on dendritic cell (DC) activation and is responsible for tumor control in vaccinated animals. Despite Doxorubicin in combination with Cyclophosphamide (A/C) is widely used to treat breast cancer patients, the stimulating effect of A/C on T and APC compartments and its correlation with patient's clinical response remains to be proved. Methods: In this prospective study, we designed an in vitro system to monitor various immunological readouts in PBMCs obtained from a total of 17 breast cancer patients before, and after neoadjuvant anti-tumor therapy with A/C. Results: The results show that before treatment, T cells and DCs, exhibit a marked unresponsiveness to in vitro stimulus: whereas T cells exhibit poor TCR internalization and limited expression of CD154 in response to anti-CD3/CD28/CD2 stimulation, DCs secrete low levels of IL-12p70 and limited CD83 expression in response to pro-inflammatory cytokines. Notably, after treatment the responsiveness of T and APC compartments was recovered, and furthermore, this recovery correlated with patients' residual cancer burden stage. Conclusions: Our results let us to argue that the model used here to monitor the T and APC compartments is suitable to survey the recovery of immune surveillance and to predict tumor response during A/C chemotherapy.

Original languageEnglish
Article number77
JournalBMC Cancer
Volume18
Issue number1
DOIs
StatePublished - 15 Jan 2018
Externally publishedYes

Keywords

  • Breast cancer
  • Chemotherapy
  • Dendritic cells
  • Doxorubicin
  • Immune-monitoring
  • Neoadjuvant
  • T cells

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