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Adenosine regulates radiation therapy-induced anti-tumor immunity

Adenosine regulates radiation therapy-induced anti-tumor immunity Wennerberg et al. Journal for ImmunoTherapy of Cancer 2015, 3(Suppl 2):P378 http://www.immunotherapyofcancer.org/content/3/S2/P378 POSTER PRESENTATION Open Access Adenosine regulates radiation therapy-induced anti-tumor immunity Erik Wennerberg , Noriko Kawashima, Sandra Demaria From 30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015) National Harbor, MD, USA. 4-8 November 2015 Radiation therapy (RT) induces immunogenic cell death T cells (MFI: 513±126 in RT+TY/23 vs 148±59 in RT, p < and dose-dependent release of ATP in the tumor microen- 0.01). TY/23 and 9H10 given alone or in combination had vironment (TME), triggering maturation and activation of no effect on tumor growth. However, each antibody tumor-resident dendritic cells (DCs). However, extracellu- potentiated tumor inhibition obtained with RT (p=0.08 for lar ATP is rapidly catabolized to adenosine by ectonucleo- RT+TY/23 and p < 0.05 for RT+9H10 vs RT). Moreover, tidases CD39 and CD73, which are expressed by tumor blockade of both CD73 and CTLA-4 in combination with cells and immune cells in the TME. Adenosine has pleio- RT further improved tumor control resulting in complete tropic immunosuppressive effects and inhibits activation tumor regression in 2/5 mice (p < 0.01 for RT+TY/23+ of DC and effector T cells, while promoting regulatory 9H10 vs RT). T cells (Tregs). Here, we tested the hypothesis that con- Our findings indicate that adenosine regulates the version of ATP to adenosine hinders generation of effec- ability of RT to induce anti-tumor immunity, affecting tive anti-tumor immunity by high dose RT, reducing its both DC maturation and T cell activation. Data suggest synergy with anti-CTLA-4 antibody. that CD73-blockade is a promising strategy to improve BALB/c mice were inoculated s.c. with 1 x 10 TSA car- synergy of RT and immunotherapy. cinoma cells on day 0 and assigned to treatment with: (1) control mAb; (2) anti-CD73 (TY/23); (3) TY/23+anti- Published: 4 November 2015 CTLA-4 (9H10); (4) RT; (5) RT+TY/23; (6) RT+9H10; (6) RT+TY/23+9H10. TY/23 (200 µg) was administered i.p. every 4 days starting on day 11. RT was given locally as doi:10.1186/2051-1426-3-S2-P378 single 20 Gy dose on day 12. 9H10 (200 µg) was given i.p. Cite this article as: Wennerberg et al.: Adenosine regulates radiation on days 11, 14 and 17. On day 18, some tumors were har- therapy-induced anti-tumor immunity. Journal for ImmunoTherapy of Cancer 2015 3(Suppl 2):P378. vested for flow cytometry analysis of DC and T cells. Mice were monitored for tumor growth/regression. In irradiated tumors, CD73-blockade reduced the per- centage of Tregs within the tumor-infiltrating CD4 T cell population (7.9±2.5% in RT+TY/23 vs 20±0.8% in RT, p < + Submit your next manuscript to BioMed Central 0.01) while increasing CD8 T cells (38.3±0.1% in RT+TY/ and take full advantage of: 23 vs 17.3±4% in RT, p < 0.05). Among intratumoral DCs + + + (CD11c MHCII ), the CD8a DC subpopulation was • Convenient online submission increased after CD73-blockade (37.9±15.7% in TY/23+RT • Thorough peer review vs 11.3±4.9% in RT, p < 0.01). Importantly, in irradiated • No space constraints or color figure charges mice, TY/23-administration enhanced activation of DCs • Immediate publication on acceptance and effector T cells, shown by increased CD40 expression • Inclusion in PubMed, CAS, Scopus and Google Scholar on CD8a DCs (MFI: 218±1 in RT+TY/23 vs 54±41 in • Research which is freely available for redistribution RT, p < 0.05) and increased CD69 expression on CD8 Submit your manuscript at Department of Pathology, New York University School of Medicine, New www.biomedcentral.com/submit York, NY, USA © 2015 Wennerberg et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal for ImmunoTherapy of Cancer Springer Journals

Adenosine regulates radiation therapy-induced anti-tumor immunity

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Publisher
Springer Journals
Copyright
Copyright © 2015 by Wennerberg et al.
Subject
Medicine & Public Health; Oncology
eISSN
2051-1426
DOI
10.1186/2051-1426-3-S2-P378
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Abstract

Wennerberg et al. Journal for ImmunoTherapy of Cancer 2015, 3(Suppl 2):P378 http://www.immunotherapyofcancer.org/content/3/S2/P378 POSTER PRESENTATION Open Access Adenosine regulates radiation therapy-induced anti-tumor immunity Erik Wennerberg , Noriko Kawashima, Sandra Demaria From 30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015) National Harbor, MD, USA. 4-8 November 2015 Radiation therapy (RT) induces immunogenic cell death T cells (MFI: 513±126 in RT+TY/23 vs 148±59 in RT, p < and dose-dependent release of ATP in the tumor microen- 0.01). TY/23 and 9H10 given alone or in combination had vironment (TME), triggering maturation and activation of no effect on tumor growth. However, each antibody tumor-resident dendritic cells (DCs). However, extracellu- potentiated tumor inhibition obtained with RT (p=0.08 for lar ATP is rapidly catabolized to adenosine by ectonucleo- RT+TY/23 and p < 0.05 for RT+9H10 vs RT). Moreover, tidases CD39 and CD73, which are expressed by tumor blockade of both CD73 and CTLA-4 in combination with cells and immune cells in the TME. Adenosine has pleio- RT further improved tumor control resulting in complete tropic immunosuppressive effects and inhibits activation tumor regression in 2/5 mice (p < 0.01 for RT+TY/23+ of DC and effector T cells, while promoting regulatory 9H10 vs RT). T cells (Tregs). Here, we tested the hypothesis that con- Our findings indicate that adenosine regulates the version of ATP to adenosine hinders generation of effec- ability of RT to induce anti-tumor immunity, affecting tive anti-tumor immunity by high dose RT, reducing its both DC maturation and T cell activation. Data suggest synergy with anti-CTLA-4 antibody. that CD73-blockade is a promising strategy to improve BALB/c mice were inoculated s.c. with 1 x 10 TSA car- synergy of RT and immunotherapy. cinoma cells on day 0 and assigned to treatment with: (1) control mAb; (2) anti-CD73 (TY/23); (3) TY/23+anti- Published: 4 November 2015 CTLA-4 (9H10); (4) RT; (5) RT+TY/23; (6) RT+9H10; (6) RT+TY/23+9H10. TY/23 (200 µg) was administered i.p. every 4 days starting on day 11. RT was given locally as doi:10.1186/2051-1426-3-S2-P378 single 20 Gy dose on day 12. 9H10 (200 µg) was given i.p. Cite this article as: Wennerberg et al.: Adenosine regulates radiation on days 11, 14 and 17. On day 18, some tumors were har- therapy-induced anti-tumor immunity. Journal for ImmunoTherapy of Cancer 2015 3(Suppl 2):P378. vested for flow cytometry analysis of DC and T cells. Mice were monitored for tumor growth/regression. In irradiated tumors, CD73-blockade reduced the per- centage of Tregs within the tumor-infiltrating CD4 T cell population (7.9±2.5% in RT+TY/23 vs 20±0.8% in RT, p < + Submit your next manuscript to BioMed Central 0.01) while increasing CD8 T cells (38.3±0.1% in RT+TY/ and take full advantage of: 23 vs 17.3±4% in RT, p < 0.05). Among intratumoral DCs + + + (CD11c MHCII ), the CD8a DC subpopulation was • Convenient online submission increased after CD73-blockade (37.9±15.7% in TY/23+RT • Thorough peer review vs 11.3±4.9% in RT, p < 0.01). Importantly, in irradiated • No space constraints or color figure charges mice, TY/23-administration enhanced activation of DCs • Immediate publication on acceptance and effector T cells, shown by increased CD40 expression • Inclusion in PubMed, CAS, Scopus and Google Scholar on CD8a DCs (MFI: 218±1 in RT+TY/23 vs 54±41 in • Research which is freely available for redistribution RT, p < 0.05) and increased CD69 expression on CD8 Submit your manuscript at Department of Pathology, New York University School of Medicine, New www.biomedcentral.com/submit York, NY, USA © 2015 Wennerberg et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Journal

Journal for ImmunoTherapy of Cancer – Springer Journals

Published: Nov 4, 2015

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