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Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

Your full name

Your affiliation information (e.g., name of your university/institution/organization)

Not displayed online.

Your Email address (not made public)

Please leave your comment to this article below.

Mathematical equations can be typed in either LaTeX formats \\[ ... \\] or $$ ... $$, or MathML format <math> ... </math>. Try the LaTeX or MathML example.

Type equation:

Preview:

Copy equation into message below

Close menu

Please click a symbol to insert it into the message box below:

Please enter the link here:

Optionally, you can enter text that should appear as linked text:

Copy link into message below

Close menu

Please enter or paste the URL to the image here (please only use links to jpg/jpeg, png and gif images):

Copy image into message below

Close menu

Type author name or keywords to filter the list of references in this group (you can add a new citation under Bibliography):

No existing citations in Discussion Group

Wikify editor is a simple editor for wiki-style mark-up. It was written by MDPI for Sciforum in 2014. The rendering of the mark-up is based on Wiky.php with some tweaks. Rendering of mathematical equations is done with MathJax. Please send us a message for support or for reporting bugs.

Close menu

Please declare any conflicts of interest you may have with this paper, financial or otherwise.

I do not have a conflict of interest

I would like to declare a conflict of interest

Display my name on the website I want to get recognition for my comment on Publons

[what’s this?]. Link your accounts here

Captcha

Renew

I accept the following conditions:

Comments must follow the standards of professional discourse and should focus on the scientific content of the article. Insulting or offensive language, personal attacks and off-topic remarks will not be permitted. Comments must be written in English. Preprints reserves the right to remove comments without notice. Readers who post comments are obliged to declare any competing interests, financial or otherwise.

Notify me about updates to this article or when a peer-reviewed version is published.

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

Abstract

Subject Areas

Comments (0)