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TMB-H - 版本历史
2026-04-18T16:36:14Z
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https://www.yiliao.com/index.php?title=TMB-H&diff=315668&oldid=prev
2026年1月25日 (日) 15:24 185.180.13.100
2026-01-25T15:24:31Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">←上一版本</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2026年1月25日 (日) 15:24的版本</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l3" >第3行：</td>
<td colspan="2" class="diff-lineno">第3行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <strong>肿瘤突变负荷</strong>（Tumor Mutational Burden, TMB），是一种通过 <strong>[[NGS]]</strong>（二代测序）技术定量的基因组生物标志物，用于反映肿瘤细胞基因组中体细胞突变的总数，通常以“每兆碱基突变数”（<strong>mut/Mb</strong>）表示。<strong>TMB-H</strong>（高肿瘤突变负荷）被认为是免疫治疗疗效的重要预测因子。其核心逻辑在于：肿瘤突变越频繁，产生的异常蛋白质（<strong>[[新抗原]]</strong> / Neoantigens）就越多，越容易被患者的免疫系统（T细胞）识别并攻击。2020年，FDA 基于 <strong>[[KEYNOTE-158]]</strong> 研究，批准 <strong>[[帕博利珠单抗]]</strong> 用于治疗 TMB-H（<strong><del class="diffchange diffchange-inline">$\ge </del>10<del class="diffchange diffchange-inline">$ </del>mut/Mb</strong>）的不可切除或转移性实体瘤患者，标志着 TMB 正式成为继 MSI-H 之后的第二个<strong>[[泛癌种]]</strong>免疫治疗伴随诊断标志物。</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <strong>肿瘤突变负荷</strong>（Tumor Mutational Burden, TMB），是一种通过 <strong>[[NGS]]</strong>（二代测序）技术定量的基因组生物标志物，用于反映肿瘤细胞基因组中体细胞突变的总数，通常以“每兆碱基突变数”（<strong>mut/Mb</strong>）表示。<strong>TMB-H</strong>（高肿瘤突变负荷）被认为是免疫治疗疗效的重要预测因子。其核心逻辑在于：肿瘤突变越频繁，产生的异常蛋白质（<strong>[[新抗原]]</strong> / Neoantigens）就越多，越容易被患者的免疫系统（T细胞）识别并攻击。2020年，FDA 基于 <strong>[[KEYNOTE-158]]</strong> 研究，批准 <strong>[[帕博利珠单抗]]</strong> 用于治疗 TMB-H（<strong><ins class="diffchange diffchange-inline">≥ </ins>10 mut/Mb</strong>）的不可切除或转移性实体瘤患者，标志着 TMB 正式成为继 MSI-H 之后的第二个<strong>[[泛癌种]]</strong>免疫治疗伴随诊断标志物。</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l29" >第29行：</td>
<td colspan="2" class="diff-lineno">第29行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">FDA 阈值</th></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">FDA 阈值</th></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong><del class="diffchange diffchange-inline">$\ge </del>10<del class="diffchange diffchange-inline">$ </del>mut/Mb</strong></td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong><ins class="diffchange diffchange-inline">≥ </ins>10 mut/Mb</strong></td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l68" >第68行：</td>
<td colspan="2" class="diff-lineno">第68行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <h3 style="margin-top: 0; color: #be123c; font-size: 1.1em;">泛癌种获批的基石</h3></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <h3 style="margin-top: 0; color: #be123c; font-size: 1.1em;">泛癌种获批的基石</h3></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin-bottom: 0; text-align: justify; font-size: 0.95em; color: #334155;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin-bottom: 0; text-align: justify; font-size: 0.95em; color: #334155;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> FDA 的批准主要基于 KEYNOTE-158 临床试验的探索性分析。该研究表明，在经治的晚期实体瘤患者中，TMB-<del class="diffchange diffchange-inline">H（$\ge </del>10<del class="diffchange diffchange-inline">$ </del>mut/Mb）组的客观缓解率（ORR）显著高于 TMB-L 组。</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> FDA 的批准主要基于 KEYNOTE-158 临床试验的探索性分析。该研究表明，在经治的晚期实体瘤患者中，TMB-<ins class="diffchange diffchange-inline">H（≥ </ins>10 mut/Mb）组的客观缓解率（ORR）显著高于 TMB-L 组。</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l80" >第80行：</td>
<td colspan="2" class="diff-lineno">第80行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;"><strong>TMB-H</strong><br>(<del class="diffchange diffchange-inline">$\ge </del>10<del class="diffchange diffchange-inline">$ </del>mut/Mb)</td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;"><strong>TMB-H</strong><br>(<ins class="diffchange diffchange-inline">≥ </ins>10 mut/Mb)</td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1; color: #166534;"><strong>29%</strong> (95% CI: 21-39)</td></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1; color: #166534;"><strong>29%</strong> (95% CI: 21-39)</td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;">具有显著的临床获益。在小细胞肺癌、宫颈癌、子宫内膜癌中表现尤为突出。</td></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;">具有显著的临床获益。在小细胞肺癌、宫颈癌、子宫内膜癌中表现尤为突出。</td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">TMB-L<br>(<del class="diffchange diffchange-inline">< </del>10 mut/Mb)</td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">TMB-L<br>(<ins class="diffchange diffchange-inline">&lt; </ins>10 mut/Mb)</td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;">6% (95% CI: 5-8)</td></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;">6% (95% CI: 5-8)</td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;">响应率极低，通常不建议单药免疫治疗（除非有 PD-L1 等其他证据）。</td></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;">响应率极低，通常不建议单药免疫治疗（除非有 PD-L1 等其他证据）。</td></div></td></tr>
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185.180.13.100
https://www.yiliao.com/index.php?title=TMB-H&diff=315667&oldid=prev
185.180.13.100：建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面
2026-01-25T15:21:59Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
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<strong>肿瘤突变负荷</strong>（Tumor Mutational Burden, TMB），是一种通过 <strong>[[NGS]]</strong>（二代测序）技术定量的基因组生物标志物，用于反映肿瘤细胞基因组中体细胞突变的总数，通常以“每兆碱基突变数”（<strong>mut/Mb</strong>）表示。<strong>TMB-H</strong>（高肿瘤突变负荷）被认为是免疫治疗疗效的重要预测因子。其核心逻辑在于：肿瘤突变越频繁，产生的异常蛋白质（<strong>[[新抗原]]</strong> / Neoantigens）就越多，越容易被患者的免疫系统（T细胞）识别并攻击。2020年，FDA 基于 <strong>[[KEYNOTE-158]]</strong> 研究，批准 <strong>[[帕博利珠单抗]]</strong> 用于治疗 TMB-H（<strong>$\ge 10$ mut/Mb</strong>）的不可切除或转移性实体瘤患者，标志着 TMB 正式成为继 MSI-H 之后的第二个<strong>[[泛癌种]]</strong>免疫治疗伴随诊断标志物。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">TMB-H / 高突变负荷</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Immune Predictive Biomarker (点击展开)</div><br />
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[[Image:TMB_Neoantigen_Mechanism.png|100px|新抗原产生示意图]]<br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">免疫原性指数</div><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">标志物类型</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">预测性标志物 (Predictive)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">FDA 阈值</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong>$\ge 10$ mut/Mb</strong></td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">检测金标准</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">全易感基因组测序 (WES)<br>FoundationOne CDx</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">关联药物</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong>[[帕博利珠单抗]]</strong> (K药)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">高发癌种</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">黑色素瘤, 肺癌, 膀胱癌</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">局限性</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;">检测平台标准化难<br>胶质瘤中预测性差</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;">生物学原理：越乱越显眼</h2><br />
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TMB-H 预测免疫疗效的生物学基础是<strong>“新抗原负荷”</strong>（Neoantigen Load）。<br />
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<li style="margin-bottom: 12px;"><strong>突变制造差异：</strong><br />
<br>癌细胞的基因突变（非同义突变）会导致其合成的蛋白质序列发生改变，产生正常细胞中没有的异常肽段。</li><br />
<li style="margin-bottom: 12px;"><strong>免疫识别的靶子：</strong><br />
<br>这些异常肽段被 MHC 分子呈递到细胞表面，成为 T 细胞识别的“靶子”。TMB 越高，靶子越多，PD-1 抑制剂解除免疫刹车后，T 细胞杀伤肿瘤的概率和强度就越大。</li><br />
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<h2 style="background: #fff1f2; color: #9f1239; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #9f1239; font-weight: bold;">临床证据：KEYNOTE-158 研究</h2><br />
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<h3 style="margin-top: 0; color: #be123c; font-size: 1.1em;">泛癌种获批的基石</h3><br />
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FDA 的批准主要基于 KEYNOTE-158 临床试验的探索性分析。该研究表明，在经治的晚期实体瘤患者中，TMB-H（$\ge 10$ mut/Mb）组的客观缓解率（ORR）显著高于 TMB-L 组。<br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">分组</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569; width: 30%;">疗效数据 (ORR)</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af; width: 45%;">临床解读</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;"><strong>TMB-H</strong><br>($\ge 10$ mut/Mb)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #166534;"><strong>29%</strong> (95% CI: 21-39)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">具有显著的临床获益。在小细胞肺癌、宫颈癌、子宫内膜癌中表现尤为突出。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">TMB-L<br>(< 10 mut/Mb)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">6% (95% CI: 5-8)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">响应率极低，通常不建议单药免疫治疗（除非有 PD-L1 等其他证据）。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">特殊例外</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #b91c1c;">无效</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[脑胶质瘤]]</strong> 和 <strong>[[EGFR突变]]</strong> 肺癌：即使 TMB 高，免疫治疗效果依然不佳（机制不同）。</td><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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[1] <strong>Marabelle A, Fakih M, Lopez J, et al. (2020).</strong> <em>Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab (KEYNOTE-158): exploratory analysis of a phase 2 clinical trial.</em> <strong>[[Lancet Oncology]]</strong>. 2020;21(10):1353-1365.<br><br />
<span style="color: #475569;">[关键证据]：TMB-H 获批的直接依据。定义了 10 mut/Mb 作为泛癌种的通用阈值，并证实了其与 PD-1 抑制剂疗效的正相关性。</span><br />
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[2] <strong>Yarchoan M, Hopkins A, Jaffee EM. (2017).</strong> <em>Tumor Mutational Burden and Response Rate to PD-1 Inhibition.</em> <strong>[[New England Journal of Medicine]]</strong>. 2017;377(25):2500-2501.<br><br />
<span style="color: #475569;">[早期发现]：绘制了著名的“线性关系图”，直观展示了不同癌种的中位 TMB 水平与其对 PD-1/PD-L1 抑制剂客观缓解率之间的强相关性。</span><br />
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[3] <strong>Chalmers ZR, Connelly CF, Fabrizio D, et al. (2017).</strong> <em>Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden.</em> <strong>[[Genome Medicine]]</strong>. 2017;9(1):34.<br><br />
<span style="color: #475569;">[全景图谱]：通过分析十万例样本，定义了不同癌种 TMB 的分布基线，发现约 10%-15% 的肿瘤属于 TMB-H。</span><br />
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TMB-H · 知识图谱<br />
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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;">关联标志物</td><br />
<td style="padding: 10px 15px; color: #334155;"><strong>[[MSI-H]]</strong> (高度重叠但不同) • <strong>[[PD-L1]]</strong> (独立预测)</td><br />
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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;">检测陷阱</td><br />
<td style="padding: 10px 15px; color: #334155;">Panel 大小需 >1 Mb • <strong>[[bTMB]]</strong> (血液TMB) 阈值尚未完全统一</td><br />
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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;">负面影响</td><br />
<td style="padding: 10px 15px; color: #334155;"><strong>[[超进展]]</strong> (HPD) 风险需警惕 • 假性进展</td><br />
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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;">未来方向</td><br />
<td style="padding: 10px 15px; color: #334155;">结合 <strong>[[GEP]]</strong> (基因表达谱) 或 STK11/KEAP1 突变进行综合评分</td><br />
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