Mima Yoshihito, Ohtsuka Tsutomu, Ebato Ippei, Nakata Yukihiro, Tsujita Akihiro, Nakazato Yoshimasa, Norimatsu Yuta
Department of Dermatology, Tokyo Metropolitan Police Hospital, Tokyo 164-8541, Japan.
Department of Dermatology, International University of Health and Welfare Hospital, Tochigi 324-8501, Japan.
Biomedicines. 2024 Aug 19;12(8):1886. doi: 10.3390/biomedicines12081886.
Immune checkpoints are mechanisms that allow cancer cells to evade immune surveillance and avoid destruction by the body's immune system. Tumor cells exploit immune checkpoint proteins to inhibit T cell activation, thus enhancing their resistance to immune attacks. Immune checkpoint inhibitors, like nivolumab, work by reactivating these suppressed T cells to target cancer cells. However, this reactivation can disrupt immune balance and cause immune-related adverse events. This report presents a rare case of prurigo nodularis that developed six months after administering nivolumab for lung adenocarcinoma. While immune-related adverse events are commonly linked to T helper-1- or T helper-17-type inflammations, T helper-2-type inflammatory reactions, as observed in our case, are unusual. The PD-1-PD-L1 pathway is typically associated with T helper-1 and 17 responses, whereas the PD-1-PD-L2 pathway is linked to T helper-2 responses. Inhibition of PD-1 can enhance PD-L1 functions, potentially shifting the immune response towards T helper-1 and 17 types, but it may also influence T helper-2-type inflammation. This study reviews T helper-2-type inflammatory diseases emerging from immune checkpoint inhibitor treatment, highlighting the novelty of our findings.
免疫检查点是癌细胞用以逃避免疫监视并避免被机体免疫系统破坏的机制。肿瘤细胞利用免疫检查点蛋白抑制T细胞活化，从而增强其对免疫攻击的抵抗力。免疫检查点抑制剂，如纳武单抗，通过重新激活这些受抑制的T细胞来靶向癌细胞发挥作用。然而，这种重新激活可能会破坏免疫平衡并导致免疫相关不良事件。本报告介绍了一例罕见的结节性痒疹病例，该病例在使用纳武单抗治疗肺腺癌六个月后出现。虽然免疫相关不良事件通常与辅助性T细胞1型或辅助性T细胞17型炎症有关，但如我们病例中所观察到的辅助性T细胞2型炎症反应并不常见。PD-1-PD-L1通路通常与辅助性T细胞1型和17型反应相关，而PD-1-PD-L2通路则与辅助性T细胞2型反应有关。抑制PD-1可增强PD-L1功能，可能使免疫反应向辅助性T细胞1型和17型转变，但也可能影响辅助性T细胞2型炎症。本研究回顾了免疫检查点抑制剂治疗引发的辅助性T细胞2型炎症性疾病，突出了我们研究结果的新颖性。
