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Circulating inflammatory proteins associate with response to immune checkpoint inhibition therapy in patients with advanced melanoma

Authors :
Niccolò Rossi
Karla A. Lee
Maria V. Bermudez
Alessia Visconti
Andrew Maltez Thomas
Laura A. Bolte
Johannes R. Björk
Laura Kist de Ruijter
Julia Newton-Bishop
Mark Harland
Heather M. Shaw
Mark Harries
Joseph Sacco
Ruth Board
Paul Lorigan
Elisabeth G.E. de Vries
Nicola Segata
Leonie S. Taams
Sophie Papa
Tim D. Spector
Paul Nathan
Rinse K. Weersma
Geke A.P. Hospers
Rudolf S.N. Fehrmann
Veronique Bataille
Mario Falchi
Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Source :
EBioMedicine, 83:104235. ELSEVIER SCIENCE BV, Rossi, N, Lee, K A, Bermudez, M V, Visconti, A, Thomas, A M, Bolte, L A, Björk, J R, de Ruijter, L K, Newton-Bishop, J, Harland, M, Shaw, H M, Harries, M, Sacco, J, Board, R, Lorigan, P, de Vries, E G E, Segata, N, Taams, L, Papa, S, Spector, T D, Nathan, P, Weersma, R K, Hospers, G A P, Fehrmann, R S N, Bataille, V & Falchi, M 2022, ' Circulating inflammatory proteins associate with response to immune checkpoint inhibition therapy in patients with advanced melanoma ', EBioMedicine, vol. 83, 104235 . https://doi.org/10.1016/j.ebiom.2022.104235
Publication Year :
2022
Publisher :
ELSEVIER SCIENCE BV, 2022.

Abstract

BACKGROUND: Inflammation can modulate tumour growth and progression, and influence clinical response to treatment. We investigated the potential of circulating inflammatory proteins for response stratification of immune checkpoint inhibitor (ICI) therapy for advanced melanoma.METHODS: Study subjects were 87 patients with unresectable stage III or IV cutaneous melanoma from the multiple centres across the United Kingdom (UK) and the Netherlands (NL) who received ipilimumab, nivolumab, or pembrolizumab, or a combination of ipilimumab and nivolumab. Serum samples were collected before and during ICI therapy at follow-up visits scheduled every third week over a 12-week period. We performed targeted quantification of 92 proteins involved in inflammation and tested for association of their pre-treatment and on-treatment levels, as well as longitudinal changes, with overall response rate, progression-free survival, and overall survival.FINDINGS: We observed consistently higher pre-treatment levels of interleukin-6 (IL-6), hepatocyte growth factor (HGF), and monocyte chemotactic protein 2 (MCP-2), in non-responders compared to responders (meta-analysis p=3.31 × 10 -4, 2.29 × 10 -4, and 1.02 × 10 -3, respectively). Patients' stratification according to the median value of IL-6, HGF, and MCP-2 highlighted a cumulative negative effect of pre-treatment levels of the three proteins on response (p=1.13 × 10 -2), with overall response rate among patients presenting with combined elevated IL-6, HGF, and MCP-2 levels being three-fold lower (26.7%) compared to patients with none of the three proteins elevated (80.0%, p=9.22 × 10 -3). Longitudinal data analysis showed that on-treatment changes in circulating inflammatory proteins are not correlated with response. INTERPRETATION: Our findings are in line with an increasing body of evidence that the pro-inflammatory cytokine IL-6 can influence response to ICI in advanced melanoma, and further support a role of circulating HGF and MCP-2 levels as prognostic biomarkers as suggested by previous smaller studies. Inflammatory proteins may serve as predictive biomarkers of ICI response and valuable targets for combination therapy.FUNDING: This work was supported by the Seerave Foundation and Dutch Cancer Society.

Details

Language :
English
ISSN :
23523964
Volume :
83
Database :
OpenAIRE
Journal :
EBioMedicine
Accession number :
edsair.doi.dedup.....5b62e91d05782c528505dc9c86b02e7c
Full Text :
https://doi.org/10.1016/j.ebiom.2022.104235