Immune checkpoint protein and cytokine expression by T lymphocytes in pleural effusion of cancer patients receiving anti-PD-1 therapy
Immune checkpoint protein and cytokine expression by T lymphocytes in pleural effusion of cancer patients receiving anti-PD-1 therapy
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DOI：
10.1016/j.lungcan.2019.10.011
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发表时间：
2019-12-01
期刊：
影响因子：
5.3
通讯作者：
Okamoto, Isamu
中科院分区：
文献类型：
--
作者：
Ikematsu, Yuki;Tanaka, Kentaro;Okamoto, Isamu
目的：在使用程序性细胞死亡-1（PD-1）或其配体PD-L1（以下称为α PD-1治疗）的抗体治疗期间，癌症患者偶尔会发生胸腔积液（PE）。此类积液通常含有浸润的单核细胞，尽管存在的免疫细胞类型以及此类患者的结局仍不清楚。材料和方法：我们进行了一项多机构观察性研究，以检查在开始后发生PE的患者的临床结局alpha PD-1治疗。我们比较了免疫细胞谱和淋巴细胞在PE的免疫状态，通过流式细胞术测定之间的9例患者谁开发的积液在α PD-1治疗（α PD-1组）和15例患者谁开发的PE治疗期间与其他抗癌药物（对照组）。与对照组相比，α PD-1组中表达免疫检查点蛋白TIM-3或TIGIT的CD 4（+）和CDS+ T淋巴细胞以及表达PD-L1的CD 8（+）T淋巴细胞的频率增加。在α PD-1组的9名患者中，有6名患者在出现PE后继续α PD-1治疗一段时间，这些患者PE中表达免疫检查点蛋白LAG-3或细胞因子白细胞介素-17的CD 4（+）T淋巴细胞的频率低于未接受持续治疗获益的患者。我们的研究结果表明，在一些发生PE的患者中继续α PD-1治疗具有临床获益。我们发现，在α PD-1治疗期间，PE中的浸润性T淋巴细胞表现出比其他癌症药物治疗期间更疲惫的表型，这些细胞的亚群以特异性免疫检查点蛋白和细胞因子表达谱为特征，可能有助于抗肿瘤免疫应答。
Objectives: Pleural effusion (PE) occasionally develops in cancer patients during treatment with antibodies to programmed cell death-1 (PD-1) or to its ligand PD-L1 (hereafter, alpha PD-1 therapy). Such effusion often contains infiltrated mononuclear cells, although the types of immune cell present as well as the outcome of such patients have remained unclear.Materials and methods: We performed a multi-institutional, observational study to examine the clinical outcome of patients who develop PE after the onset of alpha PD-1 therapy. We compared the immune cell profiles and the immune status of lymphocytes in PE as determined by flow cytometry between nine patients who developed effusion during alpha PD-1 therapy (alpha PD-1 group) and 15 patients who developed PE during treatment with other anticancer agents (control group).Results: Most mononuclear cells in PE were lymphocytes in both the alpha PD-1 and control groups. The frequency of both CD4(+) and CDS+ T lymphocytes expressing the immune checkpoint proteins TIM-3 or TIGIT as well as that of CD8(+) T lymphocytes expressing PD-L1 were increased in the alpha PD-1 group compared with the control group. alpha PD-1 therapy continued for a substantial period after the emergence of PE in six of the nine patients in the alpha PD-1 group, and the frequency of CD4(+) T lymphocytes in PE expressing the immune checkpoint protein LAG-3 or the cytokine interkeukin-17 was lower for these patients than for those who did not receive a sustained treatment benefit.Conclusion: Our results suggest a clinical benefit of continuing alpha PD-1 therapy in some patients who develop PE. We found that infiltrating T lymphocytes in PE manifest a more exhausted phenotype during alpha PD-1 therapy than during treatment with other cancer drugs, with subpopulations of these cells characterized by specific immune checkpoint protein and cytokine expression profiles possibly contributing to the antitumor immune response.