Potential oncogenic roles of mutant-p53-derived exosomes in the tumor–host interaction of head and neck cancers

Etti Ester Azulay, Tomer Cooks, Moshe Elkabets

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations


The wide-ranging collection of malignancies arising at the upper aerodigestive tract is categorized as head and neck cancer (HNC), the sixth most prevalent cancer worldwide. Infection with human papillomavirus (HPV) or exposure to carcinogens is the leading causes of HPV+ and HPV− HNCs development, respectively. HPV+ and HPV− HNCs are different in clinical and molecular aspects. Specifically, HPV− HNCs tightly associate with missense mutants of the TP53 gene (encoding for the p53 protein), suggesting a central role for mutant p53 gain-of-function (GOF) in driving tumorigenesis. In contrast, in HPV + HNC, the sequence of TP53 typically remains intact, while the protein is degraded. In tumor cells, the status of the TP53 gene affects the cargo of secreted exosomes. In this review, we describe the accumulated knowledge regarding the involvement of exosomes and p53 on cellular interactions between HPV+ and HPV− HNC cells, and the surrounding tumor microenvironment (TME). Moreover, we envision how TP53 status may determine exosomes cargo in HNC, and, consequently, modify the TME. The potential roles of exosomes described herein are based on both our studies and the studies of others on mutant p53-derived exosomes. Specifically, we showed how exosomes are shed by cancer cells harboring mutant p53 communicate with tumor-associated macrophages in the colon as well as with cancer-associated fibroblasts in the lung, creating immunosuppressive conditions and promoting invasiveness. Altogether, exosomes in HNC in the context of TP53 status are understudied and extensive research is required to shed light on the biology of HPV+ and HPV− HNC.

Original languageEnglish
Pages (from-to)285-292
Number of pages8
JournalCancer Immunology, Immunotherapy
Issue number2
StatePublished - 1 Feb 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.


This work was funded by the Israel Science Foundation (ISF, 700/16), the Concern Foundation (#7895), the United States—Israel Binational Science Foundation (BSF, #2017323), and the Israel Cancer Research Foundation (ICRF, 17-1693-RCDA) to Moshe Elkabets. Moshe Elkabets is supported by an Alon Fellowship for outstanding young researchers.

FundersFunder number
Israel Cancer Research Foundation
Concern Foundation7895
Israel Cancer Research Fund17-1693-RCDA
United States-Israel Binational Science Foundation2017323
Israel Science Foundation700/16


    • CITIM 2019
    • Exosomes
    • Head and neck
    • Human papillomavirus
    • Mutant p53
    • Tumor microenvironment


    Dive into the research topics of 'Potential oncogenic roles of mutant-p53-derived exosomes in the tumor–host interaction of head and neck cancers'. Together they form a unique fingerprint.

    Cite this