Palicelli Andrea, Croci Stefania, Bisagni Alessandra, Zanetti Eleonora, De Biase Dario, Melli Beatrice, Sanguedolce Francesca, Ragazzi Moira, Zanelli Magda, Chaux Alcides, Cañete-Portillo Sofia, Bonasoni Maria Paola, Ascani Stefano, De Leo Antonio, Giordano Guido, Landriscina Matteo, Carrieri Giuseppe, Cormio Luigi, Gandhi Jatin, Nicoli Davide, Farnetti Enrico, Piana Simonetta, Tafuni Alessandro, Bonacini Martina
Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
Biomedicines. 2022 Jan 22;10(2):236. doi: 10.3390/biomedicines10020236.
Pembrolizumab (anti-PD-1) is allowed in selected metastatic castration-resistant prostate cancer (PC) patients showing microsatellite instability/mismatch repair system deficiency (MSI-H/dMMR). loss-of-function is linked to hereditary PCs and homologous recombination DNA-repair system deficiency: poly-ADP-ribose-polymerase inhibitors can be administered to -mutated PC patients. Recently, docetaxel-refractory metastatic castration-resistant PC patients with or somatic mutations had higher response rates to pembrolizumab. regulates cell cycle/proliferation/apoptosis through pathways including the AKT/mTOR, which upregulates PD-L1 expression in PC. Our systematic literature review (PRISMA guidelines) investigated the potential correlations between PD-L1 and MMR/MSI/ statuses in PC, discussing few other relevant genes. Excluding selection biases, 74/677 (11%) PCs showed dMMR/MSI; 8/67 (12%) of dMMR/MSI cases were PD-L1+. dMMR-PCs included ductal (3%) and acinar (14%) PCs (all cases tested for MSI were acinar-PCs). In total, 15/39 (39%) PCs harbored aberrations: limited data are available for PD-L1 expression in these patients. 13/137 (10%) PTEN- PCs were PD-L1+; 10/29 (35%) PD-L1+ PCs showed PTEN negativity. mutations may increase PD-L1 levels, while the potential correlation between PD-L1 and ERG expression in PC should be clarified. Further research should verify how the efficacy of PD-1 inhibitors in metastatic castration-resistant PCs is related to dMMR/MSI, DNA-damage repair genes defects, or PD-L1 expression.
帕博利珠单抗（抗程序性死亡蛋白1）被允许用于部分显示微卫星不稳定/错配修复系统缺陷（MSI-H/dMMR）的转移性去势抵抗性前列腺癌（PC）患者。功能缺失与遗传性PC以及同源重组DNA修复系统缺陷有关：聚ADP核糖聚合酶抑制剂可用于治疗特定突变的PC患者。最近，多西他赛难治的转移性去势抵抗性PC患者中，携带特定体细胞突变的患者对帕博利珠单抗的反应率更高。其通过包括AKT/mTOR在内的信号通路调节细胞周期/增殖/凋亡，而该信号通路会上调PC中PD-L1的表达。我们的系统文献综述（遵循PRISMA指南）研究了PC中PD-L1与MMR/MSI/特定状态之间的潜在相关性，并讨论了其他一些相关基因。排除选择偏倚后，74/677例（11%）PC显示dMMR/MSI；8/67例（12%）dMMR/MSI病例为PD-L1阳性。dMMR-PC包括导管性PC（3%）和腺泡性PC（14%）（所有检测MSI的病例均为腺泡性PC）。总共15/39例（39%）PC存在特定畸变：这些患者中关于PD-L1表达的数据有限。13/137例（10%）PTEN缺陷的PC为PD-L1阳性；10/29例（35%）PD-L1阳性的PC显示PTEN阴性。特定突变可能会增加PD-L1水平，而PC中PD-L1与ERG表达之间的潜在相关性有待阐明。进一步的研究应验证PD-1抑制剂在转移性去势抵抗性PC中的疗效如何与dMMR/MSI、DNA损伤修复基因缺陷或PD-LI表达相关。
