CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational Burden and Cold Tumors.
An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational Burden and Cold Tumors.
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我们的研究结果表明，高度浸润的“热”型 EOCs 患者可从化疗中获益，而“冷”型 EOCs 的女性患者则可能需要基于 DC 的疫苗接种，以启动具有临床相关性的抗癌免疫反应。
免疫检查点抑制剂（ICI）在多种实体瘤临床管理中的成功应用，为上皮性卵巢癌（EOC）患者带来了相当大的期望。然而，由于包括有限的肿瘤突变负荷（TMB）和淋巴细胞浸润不良在内的免疫学特征，EOC对ICI反应不佳。最近，在一项纳入EOC患者的随机II期临床试验（SOV01，NCT02107937）中，一种基于自体树突状细胞（DC）的疫苗（DCVAC）已被证明是安全的，并能显著改善无进展生存期（PFS）。
我们利用测序、流式细胞术、多光谱免疫荧光显微镜和IHC，分析了SOV01研究中入组的82例患者的（治疗前）肿瘤和（治疗前及治疗后）外周血样本，旨在识别可改善接受DCVAC治疗的EOC患者临床管理的免疫生物标志物。
尽管高于中位数的TMB和丰富的CD8+ T细胞浸润与接受标准治疗化疗的EOC患者更优的临床获益相关，但在接受DCVAC的女性患者中并非如此。相反，在TMB低于中位数且CD8+ T细胞浸润稀少的患者中，观察到对DCVAC更优的临床反应。此类反应伴随着外周血中效应功能改善和肿瘤特异性细胞毒性迹象。
The successful implementation of immune checkpoint inhibitors (ICI) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunologic features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937).
We harnessed sequencing, flow cytometry, multispectral immunofluorescence microscopy, and IHC to analyze (pretreatment) tumor and (pretreatment and posttreatment) peripheral blood samples from 82 patients enrolled in SOV01, with the aim of identifying immunologic biomarkers that would improve the clinical management of patients with EOC treated with DCVAC.
Although higher-than-median TMB and abundant CD8+ T-cell infiltration were associated with superior clinical benefits in patients with EOC receiving standard-of-care chemotherapy, the same did not hold true in women receiving DCVAC. Conversely, superior clinical responses to DCVAC were observed in patients with lower-than-median TMB and scarce CD8+ T-cell infiltration. Such responses were accompanied by signs of improved effector functions and tumor-specific cytotoxicity in the peripheral blood.
Our findings suggest that while patients with highly infiltrated, "hot" EOCs benefit from chemotherapy, women with "cold" EOCs may instead require DC-based vaccination to jumpstart clinically relevant anticancer immune responses.
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