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Effect of neoadjuvant chemotherapy on immune system in patients with TNBC


A translational research project evaluating effect of chemotherapy on different immune subsets in TNBC patients from GeparNuevo trial was published in Journal for ImmunoTherapy of Cancer

Triple-negative breast cancer (TNBC) is considered the most immunogenic type of breast cancer with tumor infiltrating lymphocytes that are predictive for chemotherapy response and prognostic for patients′ survival. Many different immunotherapeutic strategies are currently explored in clinical trials for the treatment of this disease.

This study is an exploratory immune monitoring on the peripheral blood of patients with TNBC undergoing only neoadjuvant chemotherapy, namely the placebo arm of the GeparNuevo study. In brief, GeparNuevo trial is a randomized phase II double-blind placebo-controlled study randomizing patients with TNBC to durvalumab or placebo given every 4 weeks in addition to nab-paclitaxel followed by standard epirubicin and cyclophosphamide (EC). Peripheral blood was taken from 56 patients at three different time points: (i) at time of recruitment, (ii) after the first phase of treatment with nab-paclitaxel and (iii) at surgery, after the second phase treatment with EC. Multicolor flow cytometry was used to characterize changes in the immune repertoire of the patients along treatment and data were also evaluated for association with the pathological complete response (pCR) defined as ypT0 ypN0. The results demonstrated that during the first phase there were limited effects on the immune cell composition of peripheral blood, whereas a pronounced effect was shown after completing the neoadjuvant chemotherapy with EC when an almost complete loss of B cells and halving of natural killer (NK) cells as well as CD4+ T lymphocytes was detected. In contrast, CD8+ T cells as well as monocytes and granulocytes were only marginally affected by the different phases of chemotherapy. With regards to pCR, 31 out of 56 analyzed patients (54.4%) achieved a pCR after chemotherapy treatment. Comparison of biomarkers at recruitment between patients achieving a pCR (responder) and non-pCR patients (non-responder) highlighted that both the absolute numbers of NK cells in the blood as well as their frequency within the peripheral blood mononuclear cells varied among the two clinical outcomes with higher levels in the responding patients. Changes in the frequency of various immune cell populations at surgery with respect to recruitment were then evaluated for a possible association with pCR. Responding patients had a statistically significant increase in both CD4+ and CD8+ T cells expressing the exhaustion marker PD1. When the changes of markers were dichotomized into high and low and evaluated with respect to pCR, none of them showed significant correlation with clinical outcome.

In conclusion, treatment of TNBC patients with neoadjuvant nab-paclitaxel followed by EC results in an altered composition of the immune cell repertoire with B and NK cells being more affected than T cells. This might also have an impact on the combination of chemotherapies with immunotherapies.

Massa C, Karn T, Denkert C, et al. Differential effect on different immune subsets of neoadjuvant chemotherapy in patients with TNBC. J Immunother Cancer. 2020 Nov;8(2):e001261


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