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

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preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202103.0777.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

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

How to cite: Raimondi, L.; Spinelli, G. P.; Ciracì, P.; Raimondi, F. M.; Lazzeroni, R.; Benedetto, L. D.; Valabrega, S.; Giaconi, L.; Rossi, L.; Naso, G. 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. Preprints 2021, 2021030777. https://doi.org/10.20944/preprints202103.0777.v1 Raimondi, L.; Spinelli, G. P.; Ciracì, P.; Raimondi, F. M.; Lazzeroni, R.; Benedetto, L. D.; Valabrega, S.; Giaconi, L.; Rossi, L.; Naso, G. 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. Preprints 2021, 2021030777. https://doi.org/10.20944/preprints202103.0777.v1

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MDPI and ACS Style

Raimondi, L.; Spinelli, G. P.; Ciracì, P.; Raimondi, F. M.; Lazzeroni, R.; Benedetto, L. D.; Valabrega, S.; Giaconi, L.; Rossi, L.; Naso, G. 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. Preprints 2021, 2021030777. https://doi.org/10.20944/preprints202103.0777.v1

APA Style

Raimondi, L., Spinelli, G. P., Ciracì, P., Raimondi, F. M., Lazzeroni, R., Benedetto, L. D., Valabrega, S., Giaconi, L., Rossi, L., & Naso, G. (2021). 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. Preprints. https://doi.org/10.20944/preprints202103.0777.v1

Chicago/Turabian Style

Raimondi, L., Luigi Rossi and Giuseppe Naso. 2021 "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" Preprints. https://doi.org/10.20944/preprints202103.0777.v1

Abstract

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.

Keywords

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

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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