Yu Guangyang, Butler Madison K, Abdelmaksoud Abdalla, Pang Ying, Su Yu-Ting, Rae Zachary, Dadkhah Kimia, Kelly Michael C, Song Young K, Wei Jun S, Terabe Masaki, Atony Ramya, Mentges Kelly, Theeler Brett J, Penas-Prado Marta, Butman John, Camphausen Kevin, Zaghloul Kareem A, Nduom Edjah, Quezado Martha, Aldape Kenneth, Armstrong Terri S, Gilbert Mark R, Gulley James L, Khan Javed, Wu Jing
Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Front Oncol. 2021 Jan 14;10:601452. doi: 10.3389/fonc.2020.601452. eCollection 2020.
Glioma is the most common primary malignant brain tumor with a poor prognosis. Immune checkpoint inhibitors have been of great interest in investigation of glioma treatments. Here, we report single-cell transcriptomic analyses of two tumor areas from an oligodendroglioma taken from a patient who had multiple tumor recurrences, following several chemotherapies and radiation treatments. The patient subsequently received nivolumab and was considered have disease progression based on conventional diagnostic imaging after two cycles of treatment. He underwent a debulking surgical resection and pathological diagnosis was recurrent disease. During the surgery, tumor tissues were also collected from the enhancing and non-enhancing areas for a scRNAseq analysis to investigate the tumor microenvironment of these radiographically divergent areas. The scRNAseq analysis reveals a plethora of immune cells, suggesting that the increased mass observed on MRI may be partially a result of immune cell infiltration. The patient continued to receive immunotherapy after a short course of palliative radiation and remained free of disease progression for at least 12 months after the last surgery, suggesting a sustained response to immunotherapy. The scRNAseq analysis indicated that the radiological progression was in large part due to immune cell infiltrate and continued immunotherapy led to a positive clinical outcome in a patient who would have otherwise been admitted to hospice care with halting of immunotherapy. Our study demonstrates the potential of scRNAseq analyses in understanding the tumor microenvironment, which may assist the clinical decision-making process for challenging glioma cases following immunotherapy.
胶质瘤是最常见的原发性恶性脑肿瘤，预后较差。免疫检查点抑制剂在胶质瘤治疗研究中备受关注。在此，我们报告了对一名患有多灶性肿瘤复发的患者的少突胶质细胞瘤的两个肿瘤区域进行的单细胞转录组分析，该患者此前接受了多种化疗和放射治疗。该患者随后接受了纳武单抗治疗，在两个周期的治疗后，根据传统诊断成像被认为疾病进展。他接受了减瘤手术切除，病理诊断为复发性疾病。在手术过程中，还从增强和非增强区域收集了肿瘤组织用于单细胞RNA测序（scRNAseq）分析，以研究这些影像学上不同区域的肿瘤微环境。scRNAseq分析揭示了大量免疫细胞，表明磁共振成像（MRI）上观察到的肿块增加可能部分是免疫细胞浸润的结果。该患者在短程姑息性放疗后继续接受免疫治疗，最后一次手术后至少12个月无疾病进展，表明对免疫治疗有持续反应。scRNAseq分析表明，影像学进展在很大程度上是由于免疫细胞浸润，持续的免疫治疗在一名否则可能因免疫治疗停止而进入临终关怀的患者中带来了积极的临床结果。我们的研究证明了scRNAseq分析在理解肿瘤微环境方面的潜力，这可能有助于免疫治疗后具有挑战性的胶质瘤病例的临床决策过程。
