Journal Article

CD39 and LDHA affects the prognostic role of NLR in metastatic melanoma patients treated with immunotherapy

White, Andrew, Facchini, Arianna Bianca, Budillon, Alfredo, Fordellone, Mario, Chiodini, Paolo, Bailey, Michael, Ottaviano, Margaret, Sparano, Francesca, Simeone, Ester, Mallardo, Domenico, Warren, Sarah, Cesano, Alessandra, Maiolino, Piera, Cavalcanti, Ernesta, Ascierto, Paolo Antonio, Ong, Sufey, Caracò, Corrado, Church, Sarah

2023

Overview

Background Identifying response markers is highly needed to guide the treatment strategy in patients with metastatic melanoma. Methods A retrospective study was carried out in patients with unresectable/metastatic melanoma (stage IIIb–IV), treated with anti-PD-1 in the first line setting, to better explore the role and the timing of neutrophil/lymphocyte ratio (NLR) as potential biomarker of response. The relationship of NLR with inflammation-immune mediators and the underlying negative effect of raising NLR during immunotherapy, have been investigated with transcriptomic gene analysis. Results The results confirmed previous findings that a high baseline NLR is associated with a poorer prognosis and with higher serum level of lactate dehydrogenase (LDH), regardless of the presence of brain metastases. The transcriptomic analysis showed that high baseline NLR is associated with a characteristic gene signature CCNA1 , LDHA and IL18R1 , which correlates with inflammation and tumorigenesis. Conversely, low baseline NLR is associated with the signature CD3 , SH2D1A , ZAP70 and CD45RA, linked to the immune-activation. The genes positively associated with NLR ( CD39 ( ENTPD1 ), PTEN , MYD88 , MMP9 and LDH ) are involved in processes of immunosuppression, inflammation and tumor-promoting activity. Increased expression of CD39 correlated with TGFβ 2 , a marker of the N2 neutrophils with immunosuppressive activity. Conclusions These results suggest that increasing NLR is associated with an increased neutrophil population, with polarization to the N2 phenotype, and this process may be the basis for the negatively prognostic role of NLR.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Biomarker / Biomedical and Life Sciences / Biomedicine / Brain cancer / Carcinogenesis / Care and treatment / CD3 antigen / CD39 / CD45RA antigen / Cell cycle / Combination strategies / Development and progression / Discriminant analysis / Feature selection / Gelatinase B / Gene expression / Genes / Genetic aspects / HDLA / Health aspects / Immunosuppression / Immunosuppressive agents / Immunotherapy / Inflammation / L-Lactate dehydrogenase / Leukocytes (neutrophilic) / Lymphocytes / Medical prognosis / Medicine/Public Health / Melanoma / Metastases / Metastasis / MyD88 protein / Neutrophils / NLR / Patient outcomes / PD-1 protein / Phenotypes / Prognosis / PTEN protein / Response rates / SH2D1A protein / TGFβ / Transcription activation / Transcriptomics / Transforming growth factors / Tumorigenesis / Variables / ZAP-70 protein