查看“CD279”的源代码

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            <strong>[[CD279]]</strong>，即<strong>[[程序性死亡受体1]]([[PD-1]])**，是表达在激活的**[[T细胞]]</strong>、[[B细胞]]及[[髓系细胞]]表面的一种重要受体，属于<strong>[[免疫球蛋白超家族]]</strong>。作为关键的<strong>[[免疫检查点]]</strong>蛋白，[[CD279]]与其配体[[CD274]]([[PD-L1]])或[[CD273]]([[PD-L2]])结合后，会通过抑制[[T细胞]]受体信号传导来降低免疫应答强度，从而维持机体免疫稳态。然而，肿瘤细胞常利用此机制实现<strong>[[免疫逃逸]]</strong>。目前，阻断[[CD279]]通路的抗体疗法已成为恶性肿瘤临床治疗的基石，显著改善了[[黑色素瘤]]、[[非小细胞肺癌]]及[[淋巴瘤]]等多种肿瘤的生存预后。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">CD279 (PD-1)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">程序性死亡受体1·点击展开</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">分类：[[I型跨膜蛋白]]</div>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[Entrez]]ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">5133([[PDCD1]])</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">8760</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Q15116</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约32-35kDa</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">染色体定位</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2q37.3</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">主要配体</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[PD-L1]]/[[PD-L2]]</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">功能角色</th>
                    <td style="padding: 12px; color: #1e40af;">免疫抑制检查点</td>
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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;">生物学机制：免疫系统调节的“负向开关”</h2>
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        [[CD279]]通过复杂的胞内信号级联反应发挥抑制作用，防止过度的免疫反应伤害正常组织：
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        <li style="margin-bottom: 12px;"><strong>配体结合与磷酸化：</strong> 当[[CD279]]与[[PD-L1]]结合时，受体胞内段的<strong>[[ITIM]]</strong>和<strong>[[ITSM]]</strong>基序发生磷酸化。</li>
        <li style="margin-bottom: 12px;"><strong>磷酸酶招募：</strong> 磷酸化的基序招募蛋白酪氨酸磷酸酶<strong>[[SHP-2]]</strong>，后者通过脱磷酸化作用抑制<strong>[[TCR]]</strong>（T细胞受体）下游的信号转导。</li>
        <li style="margin-bottom: 12px;"><strong>代谢与增殖抑制：</strong> 阻断<strong>[[PI3K/AKT]]</strong>和<strong>[[RAS/MEK/ERK]]</strong>通路，导致[[T细胞]]活化受阻、细胞因子分泌减少，并诱导<strong>[[T细胞耗竭]]</strong>状态。</li>
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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;">临床应用：针对 CD279 的抑制剂矩阵</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">药物名称</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">厂商(主要地位)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键客观缓解与获益指标</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[帕博利珠单抗]]([[K药]])</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[MSD]](默沙东)；全球广谱免疫龙头。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">在[[NSCLC]]一线治疗中确立了 OS 获益标准。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[纳武利尤单抗]]([[O药]])</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[BMS]]；首个获批的 PD-1 抑制剂。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">在[[黑色素瘤]]及[[肾细胞癌]]中展现长效获益。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[替雷利珠单抗]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[百济神州]]；Fc 段改良国产先行者。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">在[[霍奇金淋巴瘤]]及[[胃癌]]中展现极高缓解率。</td>
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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;">诊疗策略：从单一靶向向联合免疫管理演进</h2>
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        基于[[CD279]]的治疗方案正向个体化与精准化转型：
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        <li style="margin-bottom: 12px;"><strong>标志物驱动筛选：</strong> 通过检测<strong>[[PD-L1表达]]</strong>、<strong>[[TMB]]</strong>及<strong>[[MSI-H/dMMR]]</strong>状态来预判响应可能性，实现精准给药。</li>
        <li style="margin-bottom: 12px;"><strong>垂直与水平联合：</strong> 临床广泛采用 PD-1 抑制剂联合化疗、联合抗血管药物（如[[IO+TKI]]）或联合其他免疫检查点抑制剂（如[[LAG-3]]/[[CTLA-4]]）以克服单药耐药。</li>
        <li style="margin-bottom: 12px;"><strong>irAE 规范化管理：</strong> 针对<strong>[[免疫相关不良事件]]</strong>（如免疫性肺炎、结肠炎），实施“早期监测、分级干预、激素主导”的标准化流程。</li>
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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;">关键相关概念</h2>
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            <li style="margin-bottom: 8px;"><strong>[[CD274]]([[PD-L1]])：</strong> CD279 的主要配体，其表达水平是免疫治疗的核心评估指标。</li>
            <li style="margin-bottom: 8px;"><strong>[[免疫检查点阻断]]([[ICB]])：</strong> 通过药物阻断信号轴，重新激活 [[T细胞]] 的治疗策略。</li>
            <li style="margin-bottom: 8px;"><strong>[[T细胞耗竭]]：</strong> [[CD279]] 长期高表达导致的功能衰竭状态。</li>
            <li style="margin-bottom: 8px;"><strong>[[新抗原]]([[Neoantigens]])：</strong> 与 PD-1 抑制剂效力密切相关的高免疫原性蛋白。</li>
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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>
        
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            [1] <strong>Pardoll DM. (2012).</strong> <em>The blockade of immune checkpoints in cancer immunotherapy.</em> <strong>[[Nature Reviews Cancer]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：该综述奠定了 PD-1 作为肿瘤免疫治疗核心靶点的理论基础。</span>
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            [2] <strong>Ribas A, Wolchok JD. (2018).</strong> <em>Cancer immunotherapy using checkpoint blockade.</em> <strong>[[Science]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[学术点评]：总结了 PD-1 抑制剂在实体瘤中的临床动力学特征及耐药进化模型。</span>
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            CD279 (PD-1) 诊疗生态 · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联通路</td>
                <td style="padding: 10px 15px; color: #334155;">[[PI3K/AKT]]•[[RAS/ERK]]•[[TCR信号]]•[[CD28共刺激]]•[[mTOR]]</td>
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                <td style="padding: 10px 15px; color: #334155;">[[CTLA-4]]•[[LAG-3]]•[[TIGIT]]•[[TIM-3]]•[[CD40]]•[[4-1BB]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">战略实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[SinoCellGene协作]]•[[FDA]]•[[NMPA]]•[[AACR]]•[[ASCO]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">研究前沿</td>
                <td style="padding: 10px 15px; color: #334155;">[[双抗/多抗研发]]•[[基因编辑敲除PD-1]]•[[耐药微环境重塑]]•[[新型免疫疫苗联合]]</td>
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