Immune checkpoint inhibitors (ICIs) could cause type 1 diabetes (T1D). However, the underlying mechanism remains unclear. We immunohistochemically analyzed pancreatic specimens from 3 cases with ICI-related T1D, and their histopathological data were compared those from 3 patients who had received ICI therapy but did not develop T1D (non-T1D) and 7 normal glucose-tolerant subjects as controls. All ICI-related T1D patients had susceptible HLA haplotypes. In ICI-related T1D, the β-cell area decreased and the α-cell area increased compared to non-T1D and controls. The number of CD3- positive cells around islets increased in ICI-related T1D and non-T1D compared with controls, while the number of CD68-positive cells around islets increased in ICI-related T1D compared with non-T1D and controls. The expression ratios of PD-L1 on islets decreased in non-T1D and almost completely disappeared in ICI-related T1D, while PD- L1 expression was observed in most cells of pancreatic islets in controls. This study, therefore, indicates that ICI therapy itself could reduce PD-L1 expression on islets in all subjects, which may be related to β cell vulnerability. In addition, we showed that absence of PD-L1 expression on β cells, genetic susceptibility and infiltration of macrophages as well as T lymphocytes around islets might be responsible for T1D onset.

中文翻译：

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没有 PD-L1 表达的炎症细胞浸润到胰岛与遗传易感患者中免疫检查点抑制剂相关 1 型糖尿病的发展有关

免疫检查点抑制剂 (ICI) 可能导致 1 型糖尿病 (T1D)。然而，潜在的机制仍不清楚。我们对 3 例 ICI 相关 T1D 患者的胰腺标本进行免疫组织化学分析，并将其组织病理学数据与 3 例接受 ICI 治疗但未发展为 T1D（非 T1D）的患者和 7 名正常葡萄糖耐受受试者作为对照进行比较。所有与 ICI 相关的 T1D 患者都具有易感的 HLA 单倍型。在 ICI 相关的 T1D 中，与非 T1D 和对照组相比，β 细胞面积减少，α 细胞面积增加。与对照组相比，ICI 相关 T1D 和非 T1D 患者胰岛周围 CD3 阳性细胞数量增加，而与非 T1D 和对照组相比，ICI 相关 T1D 患者胰岛周围 CD68 阳性细胞数量增加。PD-L1 在非 T1D 中的表达比例在非 T1D 中降低，在 ICI 相关的 T1D 中几乎完全消失，而在对照组的大多数胰岛细胞中观察到 PD-L1 表达。因此，本研究表明 ICI 治疗本身可以降低所有受试者胰岛 PD-L1 的表达，这可能与 β 细胞易损性有关。此外，我们发现 β 细胞上 PD-L1 表达缺失、遗传易感性和巨噬细胞浸润以及胰岛周围的 T 淋巴细胞可能是 T1D 发病的原因。