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Voluntary wheel running can lead to modulation of immune checkpoint molecule expression

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@article{1ffb87801dfd4f49b7768202e4c7d524,
title = "Voluntary wheel running can lead to modulation of immune checkpoint molecule expression",
abstract = "BACKGROUND: Exercise and physical activity (PA) are associated with reduced tumor growth and enhanced intra-tumoral immune cell infiltration in mice. We aimed to investigate the role of PA achieved by voluntary wheel running in promoting the immunogenic profile across several murine tumor models, and to explore the potential of checkpoint blockade and PA in the form of voluntary wheel running as combination therapy.MATERIAL AND METHODS: The experiments were performed with C57BL/6 mice bearing subcutaneous tumors while having access to running wheels in their cages, where key immunoregulatory molecules expressed in the tumor tissue were measured by qPCR. Furthermore, we tested the hypothesis that wheel running combined with PD-L1 -or PD-1 inhibitor treatment could lead to an additive effect on tumor growth in mice bearing B16 melanoma tumors.RESULTS: Wheel running increased immune checkpoint expression (PD-1, PD-L1, PD-L2, CD28, B7.1 and B7.2) in B16 tumor-bearing mice, while induction of only PD-L2 was found in E0771 breast cancer and Lewis Lung Cancer. In studies combining voluntary wheel running with PD-1 -and PD-L1 inhibitors we found significant effects of wheel running on attenuating B16 melanoma tumor growth, in line with previous studies. We did, however, not find an additive effect of combining either of the two immunotherapeutic treatments with access to running wheels.CONCLUSION: B16 tumors displayed upregulated expression of immune regulatory molecules and decreased tumor growth in response to PA. However, combining PA with PD-1 or PD-L1 blockade did not lead to a further augmented inhibition of tumor growth.",
keywords = "Immunotherapy, physical activity, cancer, PD1, PD-L1, Immune checkpoint molecules",
author = "Bay, {Marie Lund} and Nicole Unterrainer and Rikke Stagaard and Pedersen, {Katrine Seide} and Tim Schauer and Staffeldt, {Mie Marienhof} and Christensen, {Jesper Frank} and Pernille Hojman and Pedersen, {Bente Klarlund} and Julie Gehl",
year = "2020",
month = dec,
doi = "10.1080/0284186X.2020.1817550",
language = "English",
volume = "59",
pages = "1447--1454",
journal = "Acta Oncologica",
issn = "0284-186X",
publisher = "Informa Healthcare",
number = "12",

}

RIS

TY - JOUR

T1 - Voluntary wheel running can lead to modulation of immune checkpoint molecule expression

AU - Bay, Marie Lund

AU - Unterrainer, Nicole

AU - Stagaard, Rikke

AU - Pedersen, Katrine Seide

AU - Schauer, Tim

AU - Staffeldt, Mie Marienhof

AU - Christensen, Jesper Frank

AU - Hojman, Pernille

AU - Pedersen, Bente Klarlund

AU - Gehl, Julie

PY - 2020/12

Y1 - 2020/12

N2 - BACKGROUND: Exercise and physical activity (PA) are associated with reduced tumor growth and enhanced intra-tumoral immune cell infiltration in mice. We aimed to investigate the role of PA achieved by voluntary wheel running in promoting the immunogenic profile across several murine tumor models, and to explore the potential of checkpoint blockade and PA in the form of voluntary wheel running as combination therapy.MATERIAL AND METHODS: The experiments were performed with C57BL/6 mice bearing subcutaneous tumors while having access to running wheels in their cages, where key immunoregulatory molecules expressed in the tumor tissue were measured by qPCR. Furthermore, we tested the hypothesis that wheel running combined with PD-L1 -or PD-1 inhibitor treatment could lead to an additive effect on tumor growth in mice bearing B16 melanoma tumors.RESULTS: Wheel running increased immune checkpoint expression (PD-1, PD-L1, PD-L2, CD28, B7.1 and B7.2) in B16 tumor-bearing mice, while induction of only PD-L2 was found in E0771 breast cancer and Lewis Lung Cancer. In studies combining voluntary wheel running with PD-1 -and PD-L1 inhibitors we found significant effects of wheel running on attenuating B16 melanoma tumor growth, in line with previous studies. We did, however, not find an additive effect of combining either of the two immunotherapeutic treatments with access to running wheels.CONCLUSION: B16 tumors displayed upregulated expression of immune regulatory molecules and decreased tumor growth in response to PA. However, combining PA with PD-1 or PD-L1 blockade did not lead to a further augmented inhibition of tumor growth.

AB - BACKGROUND: Exercise and physical activity (PA) are associated with reduced tumor growth and enhanced intra-tumoral immune cell infiltration in mice. We aimed to investigate the role of PA achieved by voluntary wheel running in promoting the immunogenic profile across several murine tumor models, and to explore the potential of checkpoint blockade and PA in the form of voluntary wheel running as combination therapy.MATERIAL AND METHODS: The experiments were performed with C57BL/6 mice bearing subcutaneous tumors while having access to running wheels in their cages, where key immunoregulatory molecules expressed in the tumor tissue were measured by qPCR. Furthermore, we tested the hypothesis that wheel running combined with PD-L1 -or PD-1 inhibitor treatment could lead to an additive effect on tumor growth in mice bearing B16 melanoma tumors.RESULTS: Wheel running increased immune checkpoint expression (PD-1, PD-L1, PD-L2, CD28, B7.1 and B7.2) in B16 tumor-bearing mice, while induction of only PD-L2 was found in E0771 breast cancer and Lewis Lung Cancer. In studies combining voluntary wheel running with PD-1 -and PD-L1 inhibitors we found significant effects of wheel running on attenuating B16 melanoma tumor growth, in line with previous studies. We did, however, not find an additive effect of combining either of the two immunotherapeutic treatments with access to running wheels.CONCLUSION: B16 tumors displayed upregulated expression of immune regulatory molecules and decreased tumor growth in response to PA. However, combining PA with PD-1 or PD-L1 blockade did not lead to a further augmented inhibition of tumor growth.

KW - Immunotherapy

KW - physical activity

KW - cancer

KW - PD1

KW - PD-L1

KW - Immune checkpoint molecules

UR - http://www.scopus.com/inward/record.url?scp=85091103889&partnerID=8YFLogxK

U2 - 10.1080/0284186X.2020.1817550

DO - 10.1080/0284186X.2020.1817550

M3 - Journal article

C2 - 32935602

VL - 59

SP - 1447

EP - 1454

JO - Acta Oncologica

JF - Acta Oncologica

SN - 0284-186X

IS - 12

ER -

ID: 61949720