未经证实:胰腺导管腺癌(PDAC)是一种侵袭性恶性疾病,预后不良。尽管在多种癌症中有很高的疗效,由于诸如低肿瘤突变负担(TMB)等不利特征,免疫疗法在治疗PDAC方面几乎没有成功,低微卫星不稳定性(MSI),和非免疫原性肿瘤微环境。最近,然而,有报道称,具有高TMB和DNA错配修复缺陷(dMMR)的罕见PDAC病例对免疫治疗有阳性反应.所有这些病例都出现了林奇综合症,或MMR基因中的种系突变。
未经评估:这里,我们报告了一名57岁的男性,患有IV期PDAC,其肿瘤特征显示高TMB,高MSI,和DMMR,但与遗传性癌症相关的基因中没有种系突变,包括与Lynch综合征相关的基因。经过一系列无效的治疗,患者对ipilimumab和nivolumab联合免疫治疗呈阳性反应.据我们所知,这是一例伴有零星dMMR的高级PDAC病例的第一份报告,TMB高,没有对免疫疗法有良好反应的林奇综合症。
UNASSIGNED:该案例进一步支持TMB和高MSI/dMMR是PDAC免疫治疗的可能生物标志物,并强调了对PDAC患者进行生殖系和体细胞测试的重要性。
UNASSIGNED: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease with a poor prognosis. Despite high efficacy in multiple cancers, immunotherapy has had very little success in treating PDAC due to unfavorable characteristics such as low tumor mutational burden (TMB), low microsatellite instability (MSI), and non-immunogenic tumor microenvironment. Recently, however, there have been
reports of rare PDAC cases with high TMB and DNA mismatch repair deficiency (dMMR) that have demonstrated positive response to immunotherapy. All these cases have also presented with Lynch Syndrome, or germline mutations in MMR genes.
UNASSIGNED: Here, we report a 57-year-old male with stage IV PDAC whose tumor profile revealed high TMB, high MSI, and dMMR, but no germline mutations in genes associated with hereditary cancers including those associated with Lynch Syndrome. After a series of ineffective treatments, the patient showed positive response to combined ipilimumab and nivolumab immunotherapy. To our knowledge, this is the first report of an advanced PDAC
case with sporadic dMMR, high TMB, and no Lynch Syndrome having a good response to immunotherapy.
UNASSIGNED: This
case further supports TMB and high MSI/dMMR being possible biomarkers for immunotherapy of PDAC as well as highlights the importance of both germline and somatic testing of patients with PDAC.