Molecular and Radiological Features of Microsatellite Stable Colorectal Cancer Cases With Dramatic Responses to Immunotherapy.
Molecular and Radiological Features of Microsatellite Stable Colorectal Cancer Cases With Dramatic Responses to Immunotherapy.
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对免疫治疗有显著反应的微卫星稳定性结直肠癌病例的分子和放射学特征。
DOI：
10.21873/anticanres.15080
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发表时间：
2021-06
影响因子：
2
通讯作者：
Oh DY
中科院分区：
文献类型：
--
作者：
Keenan BP;VAN Loon K;Khilnani AD;Fidelman N;Behr SC;Atreya CE;Oh DY
大多数结直肠癌（CRC）病例具有微卫星稳定（MSS）并且不存在错配修复缺陷/微卫星不稳定性，因此对免疫治疗具有抵抗力。识别在 MSS CRC 和预测生物标志物中具有特殊反应的患者是一个需要解决的未满足的需求。我们报告了三例 MSS CRC 病例，这些病例从抗 PD-1 检查点抑制剂的免疫治疗中获得了持久的临床益处。两例病例携带 POLE P286R 突变，该突变与 MSS CRC 缺乏免疫治疗反应有关。两例患者存在共济失调毛细血管扩张突变 (ATM) 突变，这可能有助于观察到的反应，包括与一名患者联合给药的肿瘤内干扰素基因刺激剂 (STING) 通路激动剂发生相互作用。新型 DNA 损伤修复改变，包括 ATM 突变，可以深入了解基因组改变使 MSS CRC 对多种免疫疗法敏感的其他机制。
The majority of colorectal cancer (CRC) cases, which are microsatellite stable (MSS) and do not harbor mismatch repair deficiency/microsatellite instability, are resistant to immunotherapy. Identification of patients with exceptional responses in MSS CRC and predictive biomarkers is an unmet need that needs to be addressed. We report three cases of MSS CRC with durable clinical benefit from immunotherapy with anti-PD-1 checkpoint inhibitors. Two cases bear a POLE P286R mutation, which has been associated with lack of immunotherapy response in MSS CRC. Two cases bear alterations in Ataxia-Telangiectasia Mutated (ATM) which may contribute to observed responses, including interaction with a co-administered intratumoral stimulator of interferon genes (STING) pathway agonist in one patient. Novel DNA damage repair alterations, including mutations in ATM, can provide insight into additional mechanisms by which genomic alterations can sensitize MSS CRC to diverse immunotherapies.