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Abstract：
UNASSIGNED: The tumor microenvironment (TME) impacts the therapeutic efficacy of immune checkpoint inhibitors (ICIs). No liquid biomarkers are available to evaluate TME heterogeneity. Here, we investigated the clinical significance of PD-1-binding soluble PD-L1 (bsPD-L1) in gastric cancer (GC) patients and non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 blockade.
UNASSIGNED: We examined bsPD-L1, matrix metalloproteinases (MMPs), and IFN-γ levels in plasma samples from GC patients (n = 117) prior to surgery and NSCLC patients (n = 72) prior to and 2 months after ICI treatment. We also examined extracellular matrix (ECM) integrity, PD-L1 expression, and T cell infiltration in tumor tissues from 25 GC patients by Elastica Masson-Goldner staining and immunohistochemical staining for PD-L1 and CD3, respectively.
UNASSIGNED: bsPD-L1 was detected in 17/117 GC patients and 16/72 NSCLC patients. bsPD-L1 showed strong or moderate correlations with plasma MMP13 or MMP3 levels, respectively, in both GC and NSCLC patients. bsPD-L1 expression in GC was associated with IFN-γ levels and intra-tumoral T cell infiltration, whereas MMP13 levels were associated with loss of ECM integrity, allowing tumor cells to access blood vessels. Plasma MMP3 and MMP13 levels were altered during ICI treatment. Combined bsPD-L1 and MMP status had higher predictive accuracy to identify two patient groups with favorable and poor prognosis than tumor PD-L1 expression: bsPD-L1+MMP13high in GC and bsPD-L1+(MMP3 and MMP13)increased in NSCLC were associated with poor prognosis, whereas bsPD-L1+MMP13low in GC and bsPD-L1+(MMP3 or MMP13)decreased in NSCLC were associated with favorable prognosis.
UNASSIGNED: Plasma bsPD-L1 and MMP13 levels indicate T cell response and loss of ECM integrity, respectively, in the TME. The combination of bsPD-L1 and MMPs may represent a non-invasive tool to predict recurrence in GC and the efficacy of ICIs in NSCLC.
UNASSIGNED: We examined bsPD-L1, matrix metalloproteinases (MMPs), and IFN-γ levels in plasma samples from GC patients (n = 117) prior to surgery and NSCLC patients (n = 72) prior to and 2 months after ICI treatment. We also examined extracellular matrix (ECM) integrity, PD-L1 expression, and T cell infiltration in tumor tissues from 25 GC patients by Elastica Masson-Goldner staining and immunohistochemical staining for PD-L1 and CD3, respectively.
UNASSIGNED: bsPD-L1 was detected in 17/117 GC patients and 16/72 NSCLC patients. bsPD-L1 showed strong or moderate correlations with plasma MMP13 or MMP3 levels, respectively, in both GC and NSCLC patients. bsPD-L1 expression in GC was associated with IFN-γ levels and intra-tumoral T cell infiltration, whereas MMP13 levels were associated with loss of ECM integrity, allowing tumor cells to access blood vessels. Plasma MMP3 and MMP13 levels were altered during ICI treatment. Combined bsPD-L1 and MMP status had higher predictive accuracy to identify two patient groups with favorable and poor prognosis than tumor PD-L1 expression: bsPD-L1+MMP13high in GC and bsPD-L1+(MMP3 and MMP13)increased in NSCLC were associated with poor prognosis, whereas bsPD-L1+MMP13low in GC and bsPD-L1+(MMP3 or MMP13)decreased in NSCLC were associated with favorable prognosis.
UNASSIGNED: Plasma bsPD-L1 and MMP13 levels indicate T cell response and loss of ECM integrity, respectively, in the TME. The combination of bsPD-L1 and MMPs may represent a non-invasive tool to predict recurrence in GC and the efficacy of ICIs in NSCLC.
摘要：
■肿瘤微环境(TME)影响免疫检查点抑制剂(ICIs)的治疗功效。没有液体生物标志物可用于评估TME异质性。这里,我们研究了PD-1结合可溶性PD-L1(bsPD-L1)在接受PD-1/PD-L1阻断治疗的胃癌(GC)患者和非小细胞肺癌(NSCLC)患者中的临床意义.
■我们检查了bsPD-L1，基质金属蛋白酶（MMPs），和来自手术前GC患者（n=117）和ICI治疗前和后2个月NSCLC患者（n=72）的血浆样品中的IFN-γ水平。我们还检查了细胞外基质（ECM）的完整性，PD-L1表达，通过ElasticaMasson-Goldner染色和PD-L1和CD3的免疫组织化学染色，分别在25例GC患者的肿瘤组织中和T细胞浸润。
■在17/117例GC患者和16/72例NSCLC患者中检测到bsPD-L1。bsPD-L1与血浆MMP13或MMP3水平呈强或中等相关性，分别,在GC和NSCLC患者中。GC中bsPD-L1的表达与IFN-γ水平和肿瘤内T细胞浸润有关，而MMP13水平与ECM完整性的丧失有关，允许肿瘤细胞进入血管.血浆MMP3和MMP13水平在ICI治疗期间改变。结合bsPD-L1和MMP状态具有更高的预测准确性，以识别两个患者组良好和不良预后比肿瘤PD-L1表达：bsPD-L1+MMP13在GC和bsPD-L1+（MMP3和MMP13）在NSCLC中增加与不良预后相关。而GC中bsPD-L1+MMP13low和NSCLC中bsPD-L1+（MMP3或MMP13）降低与良好的预后相关。
■血浆bsPD-L1和MMP13水平表明T细胞反应和ECM完整性的丧失，分别,在TME。bsPD-L1和MMP的组合可能是预测GC复发和ICIs在NSCLC中疗效的非侵入性工具。
■我们检查了bsPD-L1，基质金属蛋白酶（MMPs），和来自手术前GC患者（n=117）和ICI治疗前和后2个月NSCLC患者（n=72）的血浆样品中的IFN-γ水平。我们还检查了细胞外基质（ECM）的完整性，PD-L1表达，通过ElasticaMasson-Goldner染色和PD-L1和CD3的免疫组织化学染色，分别在25例GC患者的肿瘤组织中和T细胞浸润。
■在17/117例GC患者和16/72例NSCLC患者中检测到bsPD-L1。bsPD-L1与血浆MMP13或MMP3水平呈强或中等相关性，分别,在GC和NSCLC患者中。GC中bsPD-L1的表达与IFN-γ水平和肿瘤内T细胞浸润有关，而MMP13水平与ECM完整性的丧失有关，允许肿瘤细胞进入血管.血浆MMP3和MMP13水平在ICI治疗期间改变。结合bsPD-L1和MMP状态具有更高的预测准确性，以识别两个患者组良好和不良预后比肿瘤PD-L1表达：bsPD-L1+MMP13在GC和bsPD-L1+（MMP3和MMP13）在NSCLC中增加与不良预后相关。而GC中bsPD-L1+MMP13low和NSCLC中bsPD-L1+（MMP3或MMP13）降低与良好的预后相关。
■血浆bsPD-L1和MMP13水平表明T细胞反应和ECM完整性的丧失，分别,在TME。bsPD-L1和MMP的组合可能是预测GC复发和ICIs在NSCLC中疗效的非侵入性工具。
