CD39和LDHA影响NLR在接受免疫疗法治疗的转移性黑色素瘤患者中的预后作用。
CD39 and LDHA affects the prognostic role of NLR in metastatic melanoma patients treated with immunotherapy.
发表日期：2023 Sep 08
作者：
Domenico Mallardo, Mario Fordellone, Andrew White, Margaret Ottaviano, Francesca Sparano, Michael Bailey, Arianna Bianca Facchini, Sufey Ong, Piera Maiolino, Corrado Caracò, Sarah Church, Ernesta Cavalcanti, Sarah Warren, Alfredo Budillon, Alessandra Cesano, Ester Simeone, Paolo Chiodini, Paolo Antonio Ascierto
来源：
Genes & Diseases
摘要：
在转移性黑色素瘤患者中，寻找反应标记物对指导治疗策略至关重要。本研究为了更好地探索中性粒细胞/淋巴细胞比值（NLR）作为潜在的反应生物标记物的角色和时机，对未切除/转移性黑色素瘤（IIIb期-IV期）患者进行了回顾性研究，这些患者接受了抗PD-1治疗。通过转录基因分析，探讨了NLR与炎症-免疫介质的关系以及免疫治疗期间NLR升高的潜在负面影响。结果证实了以前的发现，即高基线NLR与预后较差和血清乳酸脱氢酶（LDH）水平较高相关，不考虑脑转移的存在。转录组分析显示，高基线NLR与特征基因CCNA1、LDHA和IL18R1相关，这些基因与炎症和肿瘤发生相关。相反，低基线NLR与CD3、SH2D1A、ZAP70和CD45RA相关的标记，与免疫激活有关。与NLR正相关的基因（CD39（ENTPD1）、PTEN、MYD88、MMP9和LDH）参与免疫抑制、炎症和肿瘤促进活性进程。CD39表达的增加与TGFβ2正相关，TGFβ2是N2中性粒细胞的一个标记，具有免疫抑制活性。这些结果表明，NLR增加与中性粒细胞群体增加、极化到N2表型有关，这个过程可能是NLR具有负面预后作用的基础。© 2023. BioMed Central Ltd., part of Springer Nature.
Identifying response markers is highly needed to guide the treatment strategy in patients with metastatic melanoma.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.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 TGFβ2, a marker of the N2 neutrophils with immunosuppressive activity.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.© 2023. BioMed Central Ltd., part of Springer Nature.