Changes in circulating exosome molecular profiles following surgery/(chemo)radiotherapy: early detection of response in head and neck cancer patients

M.-N Theodoraki,L Hofmann,P J Schuler,T L Whiteside,T K Hoffmann,C Brunner,R Lotfi,S Laban,E K Jackson

doi:10.1038/s41416-021-01567-8

M.-N Theodoraki, L Hofmann + Show 7 more

Open Access

https://doi.org/10.1038/s41416-021-01567-8

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Abstract

BackgroundHead and neck cancers (HNSCC) are highly immunosuppressive. Plasma-derived exosomes of HNSCC patients carry immunomodulatory molecules, and their cargo correlates with clinical parameters. Here, we evaluated the exosomal molecular profile for early detection of treatment failure in locally advanced HNSCC patients treated with conventional therapy.MethodsPlasma from 17 HNSCC patients was collected before, during, and after treatment by surgery with adjuvant (chemo)radiation and at recurrence. Exosomes were isolated by size-exclusion chromatography. Total exosomal protein (TEP) was used to estimate exosome load and on-bead flow cytometry to evaluate relative fluorescence intensity (RFI) of tumour-associated and immunoregulatory proteins on exosomes. Exosomal effects on the activity of and adenosine production by T cells was assessed by flow cytometry and mass spectrometry.ResultsTEP and the ratio of tumour-/immune-cell-derived exosomes varied during and after therapy with an overall decrease in the tumour-free follow-up but an increase at recurrence. RFI values of immunoregulatory proteins on exosomes, their ability for T cell inhibition and adenosine production changed during and after therapy. PD-L1 was the earliest discriminator for treatment failure and disease-free survival.ConclusionsMonitoring of plasma exosomes during therapy represents a promising opportunity for early detection of treatment failure and risk stratification to delay/avoid recurrence.

Highlights

Head and neck cancers (HNSCC) are highly immunosuppressive
Patients As part of the non-interventional, longitudinal IRECT study (Immune Response Evaluation to Curative Conventional Therapy; NCT03053661), peripheral blood samples were obtained prospectively from 17 newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients with histologically confirmed tumours who were treated at the Head and Neck Cancer Center of the Comprehensive Cancer Center Ulm (CCCU) from 2013 to 2015 as previously described [18, 19]
The clinicopathological characteristics of the HNSCC patients stimulatory immune checkpoints, OX40 and OX40-L, carried by whose plasma was used for exosome isolation are listed in Table 1. exosomes

Summary

Introduction

Head and neck cancers (HNSCC) are highly immunosuppressive. Plasma-derived exosomes of HNSCC patients carry immunomodulatory molecules, and their cargo correlates with clinical parameters. We evaluated the exosomal molecular profile for early detection of treatment failure in locally advanced HNSCC patients treated with conventional therapy. Exosomes are the smallest (30–150 nm) extracellular vesicles (EVs) that are released by all cell types and mediate intercellular communication in physiological and pathological settings [5, 6] Due to their distinctive biogenesis in the late endosomes, their unique molecular cargo, and the ability to freely circulate in all body fluids, exosomes are of great interest as potential components of non-invasive liquid biopsy [7,8,9]. Plasma of HNSCC patients is highly enriched in tumour-cell-derived exosomes, which carry immunosuppressive proteins and are able to alter immune cell functions [10]. No studies were conducted so far in HNSCC patients receiving conventional therapy

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