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Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer
Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

Background. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chemotherapy with or without ipilimumab and to correlate them with survival.

Patients and methods. Two cohorts of SCLC patients were studied: patients treated with chemotherapy (n = 47), and patients treated with chemotherapy plus ipilimumab (n = 37). Baseline, on-treatment and after-treatment serum samples were evaluated for the presence of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, GM-CSF, and Mip-1alpha using a Luminex assay. Differential changes in cytokines between cohorts were analyzed. Associations between cytokine levels and their changes with overall survival were evaluated.

Results. Patients treated with ipilimumab showed a global increase of all cytokines after treatment initiation. A high level of IL-8 at baseline was associated with worse prognosis regardless of treatment. Baseline increased IL-2 levels predicted sensitivity to ipilimumab, while high IL-6 and TNF-alpha predicted resistance. An on-treatment increase in IL-4 levels in patients treated with immune-chemotherapy was associated with a better overall survival.

Conclusions. The addition of ipilimumab to standard chemotherapy in SCLC modulates the serum levels of cytokines. Baseline levels and their change over time relate to overall survival. Blood-based biomarkers are convenient for patients, and our results support prospective validation of cytokines as predictive biomarkers for ipilimumab in SCLC.

biomarkers, cytokines, immunotherapy, ipilimumab, small cell lung cancer
2162-4011
Hardy-Werbin, Max
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Rocha, Pedro
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Arpi, Oriol
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Taus, Álvaro
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Nonell, Lara
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Durán, Xavier
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Villanueva, Xavier
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Joseph-Pietras, Deborah
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Nolan, Luke
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Danson, Sarah
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Griffiths, Richard
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Lopez-Botet, Miguel
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Rovira, Ana
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Albanell, Joan
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Ottensmeier, Christian
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Arriola, Edurne
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Hardy-Werbin, Max
d88cf208-be13-4691-97a5-16b6c9dadf43
Rocha, Pedro
35e6ff40-2962-458f-a489-4c5078269caf
Arpi, Oriol
ede3eaa1-933d-40fa-bd29-94f94e4ccfaf
Taus, Álvaro
4c405928-4c49-457a-b511-031a07159203
Nonell, Lara
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Durán, Xavier
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Villanueva, Xavier
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Joseph-Pietras, Deborah
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Nolan, Luke
76616eba-b3a6-4d74-ad1b-db49dd8ebc01
Danson, Sarah
dc545bf0-6b2f-462d-93c2-9c9636fc3c44
Griffiths, Richard
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Lopez-Botet, Miguel
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Rovira, Ana
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Albanell, Joan
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Ottensmeier, Christian
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Arriola, Edurne
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Hardy-Werbin, Max, Rocha, Pedro, Arpi, Oriol, Taus, Álvaro, Nonell, Lara, Durán, Xavier, Villanueva, Xavier, Joseph-Pietras, Deborah, Nolan, Luke, Danson, Sarah, Griffiths, Richard, Lopez-Botet, Miguel, Rovira, Ana, Albanell, Joan, Ottensmeier, Christian and Arriola, Edurne (2019) Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer. OncoImmunology, 8 (6), [e1593810]. (doi:10.1080/2162402X.2019.1593810).

Record type: Article

Abstract

Background. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chemotherapy with or without ipilimumab and to correlate them with survival.

Patients and methods. Two cohorts of SCLC patients were studied: patients treated with chemotherapy (n = 47), and patients treated with chemotherapy plus ipilimumab (n = 37). Baseline, on-treatment and after-treatment serum samples were evaluated for the presence of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, GM-CSF, and Mip-1alpha using a Luminex assay. Differential changes in cytokines between cohorts were analyzed. Associations between cytokine levels and their changes with overall survival were evaluated.

Results. Patients treated with ipilimumab showed a global increase of all cytokines after treatment initiation. A high level of IL-8 at baseline was associated with worse prognosis regardless of treatment. Baseline increased IL-2 levels predicted sensitivity to ipilimumab, while high IL-6 and TNF-alpha predicted resistance. An on-treatment increase in IL-4 levels in patients treated with immune-chemotherapy was associated with a better overall survival.

Conclusions. The addition of ipilimumab to standard chemotherapy in SCLC modulates the serum levels of cytokines. Baseline levels and their change over time relate to overall survival. Blood-based biomarkers are convenient for patients, and our results support prospective validation of cytokines as predictive biomarkers for ipilimumab in SCLC.

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Cytokines SCLC - Accepted Manuscript
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Accepted/In Press date: 28 February 2019
e-pub ahead of print date: 27 March 2019
Keywords: biomarkers, cytokines, immunotherapy, ipilimumab, small cell lung cancer

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Local EPrints ID: 431070
URI: http://eprints.soton.ac.uk/id/eprint/431070
ISSN: 2162-4011
PURE UUID: 413d9fc3-53ed-43ca-93d7-e2b96a785603

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Date deposited: 22 May 2019 16:30
Last modified: 07 Oct 2020 06:35

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Contributors

Author: Max Hardy-Werbin
Author: Pedro Rocha
Author: Oriol Arpi
Author: Álvaro Taus
Author: Lara Nonell
Author: Xavier Durán
Author: Xavier Villanueva
Author: Deborah Joseph-Pietras
Author: Luke Nolan
Author: Sarah Danson
Author: Richard Griffiths
Author: Miguel Lopez-Botet
Author: Ana Rovira
Author: Joan Albanell
Author: Edurne Arriola

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