Modulating the tumour microenvironment using low dose radiotherapy to improve immunotherapy efficacy in mesothelioma

Synat Keam

doi:10.26182/fg1d-4y90

Modulating the tumour microenvironment using low dose radiotherapy to improve immunotherapy efficacy in mesothelioma

Synat Keam

UWA Medical School

Research output: Thesis › Doctoral Thesis

258 Downloads (Pure)

Abstract

The currently FDA approved nivolumab and ipilimumab combination is effective only in small subset of mesothelioma patients. Therefore, improved therapy is required. Here, I showed low dose radiotherapy fractionation (2 Gy × 5 fractions) transiently remodelled tumour vasculature characterised by increased vascular perfusion and reduced tumour hypoxia. This radiotherapy dose also enhanced intra-tumoural CD8+ T cell infiltration and increased gene expression associated with immunologically “hot” tumour characteristics. The combination of this radiotherapy fractionation withaPD-1/aCTLA-4 cured 100% of mesothelioma bearing mice. My finding may guide the design of radio-immunotherapy clinical trial in the next couple of years.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Cook, Alistair, Supervisor Nowak, Anna, Supervisor Ebert, Martin, Supervisor
Thesis sponsors	Australian Government Research Training Program
Award date	13 Mar 2023
DOIs	https://doi.org/10.26182/fg1d-4y90
Publication status	Unpublished - 2022

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10.26182/fg1d-4y90

THESIS - DOCTOR OF PHILOSOPHY - KEAM Synat 2022
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2 Review article
1 Article

Effects of photon radiation on DNA damage, cell proliferation, cell survival and apoptosis of murine and human mesothelioma cell lines
Keam, S., MacKinnon, K. M., Alonzo, R. A. D., Gill, S., Ebert, M. A., Nowak, A. K. & Cook, A. M., 1 Nov 2022, In: Advances in Radiation Oncology. 7, 6, 16 p., 101013.
Research output: Contribution to journal › Article › peer-review

Open Access
7 Citations (Scopus)
Immune checkpoint inhibitor therapy for malignant pleural mesothelioma
Nowak, A. K., Chin, W. L., Keam, S. & Cook, A., Dec 2021, In: Lung Cancer. 162, p. 162-168 7 p.
Research output: Contribution to journal › Review article › peer-review
5 Citations (Scopus)
Enhancing the efficacy of immunotherapy using radiotherapy
Keam, S., Gill, S., Ebert, M. A., Nowak, A. K. & Cook, A. M., 2020, In: Clinical and Translational Immunology. 9, 9, e1169.
Research output: Contribution to journal › Review article › peer-review

Open Access
50 Citations (Scopus)

Cite this

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title = "Modulating the tumour microenvironment using low dose radiotherapy to improve immunotherapy efficacy in mesothelioma",

abstract = "The currently FDA approved nivolumab and ipilimumab combination is effective only in small subset of mesothelioma patients. Therefore, improved therapy is required. Here, I showed low dose radiotherapy fractionation (2 Gy × 5 fractions) transiently remodelled tumour vasculature characterised by increased vascular perfusion and reduced tumour hypoxia. This radiotherapy dose also enhanced intra-tumoural CD8+ T cell infiltration and increased gene expression associated with immunologically “hot” tumour characteristics. The combination of this radiotherapy fractionation withaPD-1/aCTLA-4 cured 100% of mesothelioma bearing mice. My finding may guide the design of radio-immunotherapy clinical trial in the next couple of years.",

keywords = "Radiotherapy and Immunotherapy in mesothelioma",

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school = "The University of Western Australia",

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N2 - The currently FDA approved nivolumab and ipilimumab combination is effective only in small subset of mesothelioma patients. Therefore, improved therapy is required. Here, I showed low dose radiotherapy fractionation (2 Gy × 5 fractions) transiently remodelled tumour vasculature characterised by increased vascular perfusion and reduced tumour hypoxia. This radiotherapy dose also enhanced intra-tumoural CD8+ T cell infiltration and increased gene expression associated with immunologically “hot” tumour characteristics. The combination of this radiotherapy fractionation withaPD-1/aCTLA-4 cured 100% of mesothelioma bearing mice. My finding may guide the design of radio-immunotherapy clinical trial in the next couple of years.

AB - The currently FDA approved nivolumab and ipilimumab combination is effective only in small subset of mesothelioma patients. Therefore, improved therapy is required. Here, I showed low dose radiotherapy fractionation (2 Gy × 5 fractions) transiently remodelled tumour vasculature characterised by increased vascular perfusion and reduced tumour hypoxia. This radiotherapy dose also enhanced intra-tumoural CD8+ T cell infiltration and increased gene expression associated with immunologically “hot” tumour characteristics. The combination of this radiotherapy fractionation withaPD-1/aCTLA-4 cured 100% of mesothelioma bearing mice. My finding may guide the design of radio-immunotherapy clinical trial in the next couple of years.

KW - Radiotherapy and Immunotherapy in mesothelioma

U2 - 10.26182/fg1d-4y90

DO - 10.26182/fg1d-4y90

M3 - Doctoral Thesis

ER -

Modulating the tumour microenvironment using low dose radiotherapy to improve immunotherapy efficacy in mesothelioma

Abstract

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Research output

Effects of photon radiation on DNA damage, cell proliferation, cell survival and apoptosis of murine and human mesothelioma cell lines

Immune checkpoint inhibitor therapy for malignant pleural mesothelioma

Enhancing the efficacy of immunotherapy using radiotherapy

Cite this