Prediction of Response to Atezolizumab Plus Nab-Paclitaxel in Unresectable Locally Advanced Triple Negative Breast Cancer (TNBC): the ClinicalUsefulness of PD-L1 mRNA Expression in Plasma-Derived Exosomes

Lucrezia Raimondi; Gian Paolo Spinelli; Paolo Ciracì; Filippo Maria Raimondi; Rachele Lazzeroni; Laura Di Benedetto; Stefano Valabrega; Laura Giaconi; Luigi Rossi; Giuseppe Naso

doi:10.20944/preprints202103.0777.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 26 March 2021 / Approved: 31 March 2021 / Online: 31 March 2021 (15:27:45 CEST)

Patients diagnosed with unresectable locally advanced Triple Negative Breast Cancer (TNBC) usually have poor outcome for its aggressive clinical behaviour. Atezolizumab plus nanoparticle albumin-bound (nab)-Paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) among patients with unresectable locally advanced TNBC but its use is hampered by the lack of reliable predictors of tumor response. Seventy-seven consecutive patients with unresectable locally advanced TNBC treated with Atezolizumab plus nab-Paclitaxel were studied by blood draws at baseline, 28 days and 56 days after initiation of treatment. Exosomal PD-L1 mRNA in plasma was determined using Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit and objective responses were defined following the RECIST criteria v.1.1. The study evaluates whether PD-L1 mRNA copies per ml in plasma-derived exosomes may predict response to anti-PD-L1 antibodies early in the course of therapy. Our data showed patients with unresectable locally advanced TNBC and higher levels of PD-L1 mRNA expression in plasma-derived exosomes at baseline demonstrated greater response to atezolizumab plus nab-paclitaxel. Furthermore, the levels of mRNA decreased with successful treatment while the copy number increased in patients experiencing disease progression following atezolizumab plus nab-paclitaxel. For the first time, our data showed the usefulness of assessment of exosomal PD-L1 as non-invasive real-time biopsy in patients diagnosed with TNBC suggesting exosomal PD-L1 is significantly associated with outcome and response to Atezolizumab plus nab-Paclitaxel.

Exosomal PD-L1 mRNA; extracellular vesicles; Triple Negative Breast Cancer; Immunotherapy; PD-L1 axis; Atezolizumab – nab-paclitaxel; Predictive biomarkers; Liquid biopsy

LIFE SCIENCES, Biochemistry

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Prediction of Response to Atezolizumab Plus Nab-Paclitaxel in Unresectable Locally Advanced Triple Negative Breast Cancer (TNBC): the ClinicalUsefulness of PD-L1 mRNA Expression in Plasma-Derived Exosomes

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