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Upregulated glucose metabolism correlates inversely with CD8+ T-cell infiltration and survival in squamous cell carcinoma

Upregulated glucose metabolism correlates inversely with CD8+ T-cell infiltration and survival in squamous cell carcinoma
Upregulated glucose metabolism correlates inversely with CD8+ T-cell infiltration and survival in squamous cell carcinoma
Antibodies that block T cell regulatory checkpoints have recently emerged as a transformative approach to cancer treatment. However, the clinical efficacy of checkpoint blockade depends upon inherent tumor immunogenicity, with variation in infiltrating T cells contributing to differences in objective response rates. Here, we sought to understand the molecular correlates of tumor-infiltrating T lymphocytes (TIL) in squamous cell carcinoma (SCC), using a systems biologic approach to integrate publicly available omics datasets with histopathological features. We provide evidence that links TIL abundance and therapeutic outcome to the regulation of tumor glycolysis by EGFR and HIF, both of which are attractive molecular targets for use in combination with immunotherapeutics.
0008-5472
4136-4148
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Perry, Kate L.
e17623e7-e607-4f2a-a2e2-db765adaa5d1
Harden, Elena L.
25640c4c-e4f5-4558-86d5-a3f74c9c972e
Stasakova, Jana
52cf3ca8-9c3d-4754-a32e-2bfe0519c27e
Jenei, Veronika
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Fleming, Jason
0e337ac5-4c31-4ec5-bb33-2705d7dccf7f
Wood, Oliver
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Woo, Jeogmin
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Woelk, Christopher H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Thomas, Gareth J.
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Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Perry, Kate L.
e17623e7-e607-4f2a-a2e2-db765adaa5d1
Harden, Elena L.
25640c4c-e4f5-4558-86d5-a3f74c9c972e
Stasakova, Jana
52cf3ca8-9c3d-4754-a32e-2bfe0519c27e
Jenei, Veronika
04d82852-7d30-458a-bc0b-f00ae6c5dd52
Fleming, Jason
0e337ac5-4c31-4ec5-bb33-2705d7dccf7f
Wood, Oliver
b9b57016-5f60-466c-983f-38958426c4b5
Woo, Jeogmin
29d72c2b-4a91-497e-a43e-da23ac53627e
Woelk, Christopher H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de

Ottensmeier, Christian H., Perry, Kate L., Harden, Elena L., Stasakova, Jana, Jenei, Veronika, Fleming, Jason, Wood, Oliver, Woo, Jeogmin, Woelk, Christopher H., Thomas, Gareth J. and Thirdborough, Stephen M. (2016) Upregulated glucose metabolism correlates inversely with CD8+ T-cell infiltration and survival in squamous cell carcinoma. Cancer Research, 76 (14), 4136-4148. (doi:10.1158/0008-5472.CAN-15-3121). (PMID:27206847)

Record type: Article

Abstract

Antibodies that block T cell regulatory checkpoints have recently emerged as a transformative approach to cancer treatment. However, the clinical efficacy of checkpoint blockade depends upon inherent tumor immunogenicity, with variation in infiltrating T cells contributing to differences in objective response rates. Here, we sought to understand the molecular correlates of tumor-infiltrating T lymphocytes (TIL) in squamous cell carcinoma (SCC), using a systems biologic approach to integrate publicly available omics datasets with histopathological features. We provide evidence that links TIL abundance and therapeutic outcome to the regulation of tumor glycolysis by EGFR and HIF, both of which are attractive molecular targets for use in combination with immunotherapeutics.

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Accepted/In Press date: 24 April 2016
e-pub ahead of print date: 20 May 2016
Published date: 15 July 2016
Organisations: Cancer Sciences

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Local EPrints ID: 396154
URI: http://eprints.soton.ac.uk/id/eprint/396154
ISSN: 0008-5472
PURE UUID: 2b84f17c-ee68-4279-868d-a0eb57341c57

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Date deposited: 07 Jun 2016 09:08
Last modified: 15 Mar 2024 05:37

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Contributors

Author: Kate L. Perry
Author: Elena L. Harden
Author: Jana Stasakova
Author: Veronika Jenei
Author: Jason Fleming
Author: Oliver Wood
Author: Jeogmin Woo
Author: Christopher H. Woelk

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