Abstract
BackgroundVaccination 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.MethodsIn 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.ResultsThe 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.ConclusionsOur 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.
Highlights
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
The monitoring of tumor response in 17 patients with breast cancer (BC) during neoadjuvant chemotherapy showed that after treatment pathological complete response observed in four of 17 patients, with a tumor shrinkage in 16/17 patients who experienced a significant reduction in tumor area (Fig. 1a)
Based on tumor response in this cohort, we explored the behavior of different immunological readouts before and after chemotherapy that could be associated with the clinical response
Summary
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. Clinical evidence on the immunogenicity of tumors induced by anti-tumor therapy has shown that a good clinical response to Doxorubicin is correlated with changes in immune contexture of the tumor [3, 4]. The efforts to demonstrate a relationship between immunogenicity of tumors induced by chemotherapy and anti-tumor immune signatures in breast cancer (BC) patients with clinical. Bernal-Estévez et al BMC Cancer (2018) 18:77 response to treatment have yielded some evidence in this direction [6, 7]. Despite, these studies for the identification of biomarkers with the potential to predict chemotherapeutic responses in BC are encouraging, blood-based monitoring systems to predict clinical response to treatment does not exist. In the case of BC patients under neoadjuvant therapy, the identification of predictive markers of clinical response using whole blood or PBMCs is desirable because this would help the adjustment of the chemotherapy regimes in trying to achieve pathological complete responses (pCR) in all patients treated
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