Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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
* ORCID logo ,
Gian Paolo Spinelli
ORCID logo ,
Paolo Ciracì
,
Filippo Maria Raimondi
,
Rachele Lazzeroni
,
Laura Di Benedetto
,
Stefano Valabrega
,
Laura Giaconi
,
Luigi Rossi
,
Giuseppe Naso
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

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.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.