Slotta-Huspenina Julia, Schwamborn Kristina, Steiger Katja, Simon Ricarda, Kirchhoff Florian Paul, Büchler Jakob Wolf, Fiedler Julia, Retz Margitta, Nawroth Roman, Ritschel Christoph, Gschwend Jürgen Erich, Horn Thomas
Institute of Pathology, Technical University of Munich, Munich, Germany.
Department of Urology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
Bladder Cancer. 2022 Sep 15;8(3):269-276. doi: 10.3233/BLC-211604. eCollection 2022.
Loss of MHC I expression is a tumoral escape mechanism, part of the process of immunoediting. MHC expression patterns and their prognostic and predictive value have not been studied in urothelial carcinoma of the bladder (UC) so far.
To correlate the expression of MHC I and MHC II with prognosis after curative treatment, response to chemotherapy and checkpoint inhibition.
We analyzed different patient cohorts for their expression of MHC I(HLA-A/B/C) and II (HLA-DR/DP/DQ) and examined potential correlations with prognosis and response to cisplatin-based chemotherapy or PD-1/PD-L1 directed immunotherapy.
Overall, MHC expression was analyzed in 246 patients, and complete MHC I loss was seen in 29.7% of patients. In 35% of patients aberrant tumoral expression of MHC II was observed. In a homogeneous cohort of 149 patients with cystectomy with curative intent there were no significant differences in survival between the MHC expression groups. MHC I+ and MHC II+ patients had higher infiltration densities with CD8+ T effector cells.An analysis of 77 additional patients (cohort II) with neoadjuvant chemotherapy revealed no associations of MHC status with response defined as < pT2 pN0 in the cystectomy specimen. Lastly, we analyzed 26 patients with metastatic disease treated with PD-1/PD-L1 directed immunotherapy (cohort III, best response: 11 PD, 5 SD, 10 OR) and observed responses exclusively in MHC I+ patients (10/19 patients, 52.6). All four MHC I+ /MHC II+ /PD-L1+ patients had a progression-free interval of at least 12 months.
Tumoral MHC I expression is frequently lost in UC. We found no association with prognosis or response to cisplatin-based chemotherapy but response to checkpoint inhibitors was limited to MHC I+ patients.
主要组织相容性复合体I（MHC I）表达缺失是一种肿瘤逃逸机制，是免疫编辑过程的一部分。迄今为止，尚未对膀胱尿路上皮癌（UC）中的MHC表达模式及其预后和预测价值进行研究。
将MHC I和MHC II的表达与根治性治疗后的预后、化疗反应和检查点抑制反应相关联。
我们分析了不同患者队列中MHC I（HLA-A/B/C）和II（HLA-DR/DP/DQ）的表达情况，并研究了其与预后以及对基于顺铂的化疗或PD-1/PD-L1定向免疫治疗反应的潜在相关性。
总体而言，对246例患者的MHC表达进行了分析，29.7%的患者出现了MHC I完全缺失。35%的患者观察到MHC II的异常肿瘤表达。在149例有治愈意图的膀胱切除术患者的同质队列中，MHC表达组之间的生存率无显著差异。MHC I+和MHC II+患者的CD8+T效应细胞浸润密度更高。对另外77例接受新辅助化疗的患者（队列II）的分析显示，MHC状态与膀胱切除标本中定义为<pT2 pN0的反应无关联。最后，我们分析了26例接受PD-1/PD-L1定向免疫治疗的转移性疾病患者（队列III，最佳反应：11例疾病进展，5例疾病稳定，10例客观缓解），仅在MHC I+患者中观察到反应（19例患者中的10例，52.6%）。所有4例MHC I+/MHC II+/PD-L1+患者的无进展生存期至少为12个月。
UC中肿瘤MHC I表达经常缺失。我们发现其与预后或基于顺铂的化疗反应无关，但检查点抑制剂的反应仅限于MHC I+患者。
