Meireson Annabel, Tavernier Simon J, Van Gassen Sofie, Sundahl Nora, Demeyer Annelies, Spaas Mathieu, Kruse Vibeke, Ferdinande Liesbeth, Van Dorpe Jo, Hennart Benjamin, Allorge Delphine, Haerynck Filomeen, Decaestecker Karel, Rottey Sylvie, Saeys Yvan, Ost Piet, Brochez Lieve
Cancer Research Institute Ghent (CRIG), Ghent University, 9000 Ghent, Belgium.
Dermatology Research Unit, Ghent University Hospital, 9000 Ghent, Belgium.
Cancers (Basel). 2021 May 27;13(11):2630. doi: 10.3390/cancers13112630.
(1) Background: Blockade of the PD-1/PD-L1 pathway has revolutionized the oncology field in the last decade. However, the proportion of patients experiencing a durable response is still limited. In the current study, we performed an extensive immune monitoring in patients with stage III/IV melanoma and stage IV UC who received anti-PD-1 immunotherapy with SBRT. (2) Methods: In total 145 blood samples from 38 patients, collected at fixed time points before and during treatment, were phenotyped via high-parameter flow cytometry, luminex assay and UPLC-MS/MS. (3) Results Baseline systemic immunity in melanoma and UC patients was different with a more prominent myeloid compartment and a higher neutrophil to lymphocyte ratio in UC. Proliferation (Ki67) of CD8 T-cells and of the PD-1/PD-L1 CD8 subset at baseline correlated with progression free survival in melanoma. In contrast a higher frequency of PD-1/PD-L1 expressing non-proliferating (Ki67) CD8 and CD4 T-cells before treatment was associated with worse outcome in melanoma. In UC, the expansion of Ki67 CD8 T-cells and of the PD-L1 subset relative to tumor burden correlated with clinical outcome. (4) Conclusion: This study reveals a clearly different immune landscape in melanoma and UC at baseline, which may impact immunotherapy response. Signatures of proliferation in the CD8 T-cell compartment prior to and early after anti-PD-1 initiation were positively correlated with clinical outcome in both cohorts. PD-1/PD-L1 expression on circulating immune cell subsets seems of clinical relevance in the melanoma cohort.
(1) 背景：在过去十年中，PD-1/PD-L1通路的阻断彻底改变了肿瘤学领域。然而，出现持久反应的患者比例仍然有限。在本研究中，我们对接受立体定向体部放疗（SBRT）联合抗PD-1免疫治疗的III/IV期黑色素瘤患者和IV期尿路上皮癌（UC）患者进行了广泛的免疫监测。(2) 方法：在治疗前和治疗期间的固定时间点，从38例患者中总共采集了145份血样，通过高参数流式细胞术、液相芯片分析和超高效液相色谱-串联质谱法（UPLC-MS/MS）进行表型分析。(3) 结果：黑色素瘤和UC患者的基线全身免疫不同，UC患者的髓系区室更突出，中性粒细胞与淋巴细胞比值更高。基线时CD8 T细胞以及PD-1/PD-L1 CD8亚群的增殖（Ki67）与黑色素瘤患者的无进展生存期相关。相反，治疗前表达PD-1/PD-L1的非增殖性（Ki67）CD8和CD4 T细胞频率较高与黑色素瘤患者预后较差相关。在UC中，Ki67 CD8 T细胞和PD-L1亚群相对于肿瘤负荷的扩增与临床结果相关。(4) 结论：本研究揭示了黑色素瘤和UC在基线时明显不同的免疫格局，这可能影响免疫治疗反应。在两个队列中，抗PD-1治疗开始前和早期CD8 T细胞区室中的增殖特征与临床结果呈正相关。循环免疫细胞亚群上的PD-1/PD-L1表达在黑色素瘤队列中似乎具有临床相关性。
