在错配修复等位基因完整/微卫星稳定的转移性结直肠癌中优化免疫联合疗法

MGMT甲基化的pMMR mCRC病患者换用替莫唑胺诱导2个年底，然后重新组建伊匹木嘌呤/纳武利成之嘌呤对这种治疗展开了研究者，交果辨识重度预处理病患者的合理率为43%[18]。这项研究者是否选择了在重新组建病原体放射治疗之前较强良好疾病病理学交构上的病患者唯不确实。与烷基化剂一样，PARP可也可以一连串这种同上现型，目之前即将展开实验研究者。

TAM可导致病原体可抑制普遍性TME。虽然M1巨噬蛋白质一连串坏死，但M2同上现型愈来愈具病原体可抑制功用。一些载体药物，如瑞戈非尼；大伐替尼，可以降低M2的暗示，促进M1分化[19,20]。瑞戈非尼和纳武利成之嘌呤重新组建使用在日本线或或后线放射治疗的pMMR mCRC病患者之中辨识成活普遍性，在这种治疗难治普遍性环境之中，ORR为36%，mPFS为7.9个年底[21]。除1唯病患者外，所有有应答的病患者均患有pMMR mCRC，在这项1b期研究者之中辨识成合理普遍性回波。然而，在北美人群之中，这种一组并未辨识成合理普遍性，ORR为7%[22]。无肝转移的病患者只不过从这种一组之中获益最多，ORR为21%。此外，与瑞戈非尼相对于，在pMMR mCRC治疗难治普遍性环境之中，使用阿替利珠嘌呤和考比替尼（cobimetinib）的这种重新组建治疗并未辨识成合理普遍性[16]。乐伐替尼和托博利珠嘌呤的重新组建治疗即将展开3期研究者（NCT04776148）。

这些研究者包括了ICIs显然在pMMR mCRC之中合理的回波；然而，还能够愈来愈多的数据和一新放射治疗方法。

何为合理的病原体放射治疗一组？

目之前在临床实践之中，对于pMMR mCRC唯不合理的ICI重新组建放射治疗。然而，目之前有几项实验即将研究者基于pMMR mCRC临床之前病理学研究者的新一组。

多臂CheckMate-142研究者（NCT02060188）即将指标纳武利成之嘌呤重新组建伊匹木嘌呤、relatlimab（外用LAG3外用体）和Daratumab（CD38外用体）的功用。暗示CD38的骨髓外充质干蛋白质在pMMR-mCRC之中较强病原体可抑制功用，载体这些蛋白质可诱导对ICIs敏感的坏死恶普遍性。iSCORE研究者（NCT03867799）也在指标relatlimab和纳武利成之嘌呤在无治疗提议之中对经EGFR可放射治疗后健康状况令人满意的pMMR mCRC病患者的影响。这项研究者是基于的临床之前数据辨识，暴露于EGFR可后LAG3（可抑制普遍性T蛋白质蛋白）升至；而对其阻断显然会一连串病原体坏死同上现型[23]。

为何pMMR mCRC对ICI并未的病理学根基即将研究者之中，而即将研究者之中的ICI一组辨识成较强良好的药效。pMMR mCRC放射治疗的未来显然会将病原体治疗与其他系统化外用恶普遍性治疗辅以，但最佳一组仍不确实。

来源

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