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The role of biomarkers for the prediction of response to checkpoint immunotherapy and the rationale for the use of checkpoint immunotherapy in cervical cancer

Otter, Sophie, Chatterjee, Jayanta, Stewart, Alexandra and Michael, Agnieszka (2019) The role of biomarkers for the prediction of response to checkpoint immunotherapy and the rationale for the use of checkpoint immunotherapy in cervical cancer Clinical Oncology.

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Abstract

Background

Checkpoint immunotherapy has revolutionised the way that melanoma is treated and has also shown significant effectiveness in lung, bladder, renal and head and neck cancers. At the present time, trials of checkpoint immunotherapy are at early phases in cervical cancer but there is very good rationale for pursuing this as a treatment option especially as cervical cancer is a virally driven cancer and therefore should be recognised by the immune system as being foreign. This review explores the biomarkers for the selection of patients for immunotherapy in other cancers such as PD-L1 expression, tumour infiltrating lymphocytes and total mutational burden and relates these biomarkers to cervical cancer.

Design

A PubMed search for publications published in English with the terms “immunotherapy” OR “cervical cancer” OR “checkpoint blockade” OR “tumour infiltrating lymphocytes” OR ‘total mutational burden”. Articles that met these criteria and were available on PubMed before October 8, 2018, were included.

Results

PD-L1 is positive in up to 90% of cervical cancers and the total mutational burden is moderately high with 5-6 mutations per megabase. In addition, the tumour microenvironment in cervical cancer has an impact on prognosis with higher ratios of CD8+ tumour infiltrating lymphocytes (TILs) to CD4+ T regulatory cells being associated with improved survival. Clinical studies to date have shown the response rate of cervical cancer to checkpoint immunotherapy to be in the region to 10-25%.

Conclusion

Cervical cancer exhibits many of the features that have been shown to be correlated with response to checkpoint immunotherapy in other tumour sites. However, response rates to date are in the region of 10-25%. Therefore, combinations of immunotherapeutic agents or checkpoint inhibitors with radiotherapy may be required to maximise the therapeutic benefit of harnessing the host immune system to fight cancer.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Otter, Sophies.otter@surrey.ac.uk
Chatterjee, Jayanta
Stewart, Alexandra
Michael, AgnieszkaA.Michael@surrey.ac.uk
Date : 2019
Copyright Disclaimer : © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Related URLs :
Depositing User : Clive Harris
Date Deposited : 17 Jul 2019 08:43
Last Modified : 22 Jul 2019 07:08
URI: http://epubs.surrey.ac.uk/id/eprint/852257

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