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<strong>CD274</strong>，临床上更为人熟知的名称是 <strong>PD-L1</strong> (Programmed Death-Ligand 1) 或 B7-H1，编码一种跨膜免疫检查点蛋白。作为 T 细胞表面受体 <strong>[[PDCD1]]</strong> (PD-1) 的主要配体，CD274 的结合会向 T 细胞传递一种“负性调节信号”，导致 T 细胞耗竭（Exhaustion）并抑制其杀伤功能。在肿瘤生物学中，肿瘤细胞通过异常高表达 CD274 来“伪装”自己，从而逃避免疫系统的监视与清除（即免疫逃逸）。靶向阻断 PD-1/PD-L1 轴的免疫疗法已彻底改变了晚期癌症的治疗格局，成为继手术、放化疗后的第四大癌症治疗支柱。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">CD274 (PD-L1) · 基因档案</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Gene & Protein Profile (点击展开)</div><br />
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[[文件:PDL1_PD1_Interaction.png|100px|PD-L1 与 PD-1 结合示意图]]<br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">免疫检查点配体</div><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc; width: 40%;">基因符号</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;"><strong>CD274</strong></td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">常用别名</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">PD-L1, B7-H1</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">编码蛋白</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">Programmed death-ligand 1</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">染色体位置</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">9p24.1</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">Entrez ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">29126</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">HGNC ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">17635</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">UniProt</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">Q9NZQ7</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">分子量</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">~33 kDa (糖基化后 ~50kDa)</td><br />
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<th style="text-align: left; padding: 8px 12px; color: #475569; background-color: #f8fafc;">药物靶点</th><br />
<td style="padding: 8px 12px; color: #0f172a;">ICIs (Atezolizumab等)</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制：免疫刹车与适应性抵抗</h2><br />
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CD274 属于免疫球蛋白超家族，其功能核心在于调控外周组织的免疫耐受。<br />
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<li style="margin-bottom: 12px;"><strong>分子握手 (Molecular Handshake)：</strong> 当肿瘤细胞或抗原呈递细胞（APC）表面的 PD-L1 与 T 细胞表面的 PD-1 结合时，会招募磷酸酶 <strong>SHP-2</strong>，去磷酸化 TCR 通路中的关键激酶（如 ZAP70），从而阻断 T 细胞的活化信号。这就像是踩下了免疫反应的“刹车”。</li><br />
<li style="margin-bottom: 12px;"><strong>适应性免疫抵抗 (Adaptive Immune Resistance)：</strong> 有趣的是，PD-L1 的表达往往并非肿瘤细胞“固有”的，而是对免疫攻击的反应。浸润肿瘤的 T 细胞分泌 <strong>[[干扰素-γ]] (IFN-γ)</strong> 试图杀伤肿瘤，但 IFN-γ 同时通过 JAK-STAT 通路诱导肿瘤细胞上调 PD-L1 表达。这是肿瘤利用免疫系统的自身机制进行反向抑制的经典案例。</li><br />
<li style="margin-bottom: 12px;"><strong>组成性驱动：</strong> 在某些淋巴瘤（如经典霍奇金淋巴瘤）中，9p24.1 染色体扩增直接导致 PD-L1 基因拷贝数增加和过表达，而不依赖于外部信号。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床景观：伴随诊断与生物标志物</h2><br />
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CD274 不仅是治疗靶点，其在肿瘤组织中的表达水平（IHC 染色）也是决定患者是否适用免疫治疗的关键<strong>生物标志物 (Biomarker)</strong>。<br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">癌种</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">评分系统</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">非小细胞肺癌 (NSCLC)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">TPS (Tumor Proportion Score)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>TPS ≥ 50%</strong>：一线单药使用帕博利珠单抗（K药）的金标准。<br>TPS 1-49%：通常建议联合化疗。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">胃癌 / 食管癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">CPS (Combined Positive Score)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">综合了肿瘤细胞和免疫细胞的表达。CPS ≥ 5 或 10 是纳武利尤单抗（O药）等药物获批的门槛。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">经典霍奇金淋巴瘤 (cHL)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">基因扩增 (9p24.1 Amp)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">几乎所有病例均有 PD-L1 过表达。对 PD-1 阻断剂极其敏感，客观缓解率（ORR）极高。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">三阴性乳腺癌 (TNBC)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">IC (Immune Cells) 评分</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">评估浸润免疫细胞的 PD-L1 表达，用于指导阿替利珠单抗等药物的使用（特定适应症）。</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">治疗策略：免疫检查点抑制剂 (ICIs)</h2><br />
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靶向 PD-1/PD-L1 轴的单克隆抗体分为两类：直接结合 PD-L1 的和结合其受体 PD-1 的。<br />
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<li style="margin-bottom: 12px;"><strong>Anti-PD-L1 抗体：</strong><br />
<br>代表药物：<strong>[[Atezolizumab]]</strong> (阿替利珠单抗), <strong>[[Durvalumab]]</strong> (度伐利尤单抗), <strong>[[Avelumab]]</strong>。<br />
<br><span style="font-size: 0.9em; color: #64748b;">*特点：直接阻断 PD-L1，但保留 PD-L2 与 PD-1 的结合（可能保留轻微的免疫抑制以减少自身免疫副作用）。Durvalumab 是 III 期肺癌巩固治疗的标准方案（PACIFIC 模式）。</span><br />
</li><br />
<li style="margin-bottom: 12px;"><strong>Anti-PD-1 抗体：</strong><br />
<br>代表药物：<strong>[[Pembrolizumab]]</strong> (帕博利珠单抗), <strong>[[Nivolumab]]</strong> (纳武利尤单抗)。<br />
<br><span style="font-size: 0.9em; color: #64748b;">*机制：结合 T 细胞上的 PD-1 受体，同时阻断 PD-L1 和 PD-L2 的结合。临床适应症最广，被称为“广谱抗癌药”。</span><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">关键关联概念</h2><br />
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<li style="margin-bottom: 12px;"><strong>PDCD1 (PD-1)：</strong> CD274 的受体，表达于活化的 T 细胞上。</li><br />
<li style="margin-bottom: 12px;"><strong>免疫逃逸 (Immune Evasion)：</strong> 肿瘤细胞通过上调 PD-L1 躲避免疫杀伤的过程。</li><br />
<li style="margin-bottom: 12px;"><strong>TPS / CPS / IC：</strong> 评估 PD-L1 表达水平的三种主要病理评分标准。</li><br />
<li style="margin-bottom: 12px;"><strong>微卫星不稳定性 (MSI-H)：</strong> 具有 MSI-H 特征的肿瘤通常具有高突变负荷和高 PD-L1 表达，对免疫治疗反应极佳。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[1] <strong>Dong H, et al. (1999).</strong> <em>Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.</em> <strong>Nature Medicine</strong>. <br><br />
<span style="color: #475569;">[学术点评]：陈列平教授团队的开创性工作。首次克隆了 B7-H1 (PD-L1)，并提出了肿瘤利用它诱导 T 细胞凋亡进行免疫逃逸的概念。</span><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[2] <strong>Freeman GJ, et al. (2000).</strong> <em>Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.</em> <strong>Journal of Experimental Medicine</strong>. <br><br />
<span style="color: #475569;">[学术点评]：确立了 PD-L1 与 PD-1 的配体-受体关系，并证实其抑制 T 细胞活化的功能。</span><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[3] <strong>Topalian SL, et al. (2012).</strong> <em>Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.</em> <strong>New England Journal of Medicine (NEJM)</strong>. <br><br />
<span style="color: #475569;">[学术点评]：免疫治疗的“登月时刻”。报道了 Anti-PD-1 在多种实体瘤中的持久疗效，开启了免疫肿瘤学（IO）的新纪元。</span><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[4] <strong>Brahmer JR, et al. (2012).</strong> <em>Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.</em> <strong>New England Journal of Medicine (NEJM)</strong>. <br><br />
<span style="color: #475569;">[学术点评]：与 Topalian 研究同期发表，证实了直接靶向配体 PD-L1 (BMS-936559) 同样具有广泛的抗肿瘤活性。</span><br />
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[5] <strong>Garon EB, et al. (2015).</strong> <em>Pembrolizumab for the treatment of non-small-cell lung cancer.</em> <strong>New England Journal of Medicine (NEJM)</strong>. <br><br />
<span style="color: #475569;">[学术点评]：KEYNOTE-001 研究。确立了 PD-L1 表达水平（TPS score）作为非小细胞肺癌疗效预测标志物的地位。</span><br />
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<div style="background-color: #0f172a; color: #ffffff; text-align: center; font-weight: bold; padding: 10px; letter-spacing: 1px;">CD274 · 知识图谱关联</div><br />
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[[PDCD1]] • [[免疫检查点抑制剂]] • [[非小细胞肺癌]] • [[干扰素-γ]] • [[霍奇金淋巴瘤]] • [[Atezolizumab]] • [[Pembrolizumab]] • [[微卫星不稳定性]]<br />
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