Fatima Merium, Bashir Shaarif, Raza Syed Atif, Hassan Muhammad, Abu Bakar Muhammad, Sheikh Ali Zafar, Tahseen Muhammad, Sheikh Umer Nisar, Loya Asif, Faisal Muhammad, Farooq Asim, Asghar Kashif
Department of Pharmacy, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan.
Punjab University College of Pharmacy, University of The Punjab, Lahore, Pakistan.
Front Oncol. 2025 Aug 12;15:1495722. doi: 10.3389/fonc.2025.1495722. eCollection 2025.
BACKGROUND: Tongue squamous cell carcinoma (TSCC) is a significant global health issue with high incidence and mortality rates. Current treatments involve surgery, radiotherapy, and chemotherapy; however, prognosis remains poor. Recent research highlights the crucial role of the tumor microenvironment, especially immune cells and checkpoints like PD-L1 and IDO, in TSCC progression. AIM: This study aims to investigate the expression of IDO and PD-L1 in TSCC patients before and after chemotherapy and their association with patients' clinicopathological characteristics. MATERIALS AND METHODS: This study involved 106 TSCC patients from Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Pakistan, with biopsies obtained from 2012 to 2022. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded (FFPE) tumor samples to evaluate IDO and PD-L1 expression before and after chemotherapy. Data on patient demographics, tumor characteristics, and treatment were collected, and follow-up continued until January 2024. RESULTS: The cohort had a mean age of 48.9 years, with a predominance of male patients. Prior to chemotherapy, 83% of patients were IDO-negative, and 75.5% were PD-L1-negative. Post-chemotherapy, IDO expression increased to 24.5% of patients (n = 26), with 84.6% exhibiting low expression and 15.4% showing high expression. While PD-L1 expression was increased to 29.2% (n = 31), with 90.3% of the positive cases showing low expression and 9.7% high expression. IDO expression was notably higher in multifocal tumors and correlated with increased comorbidities post-chemotherapy. Despite changes in marker expression, there was no significant difference in survival rates associated with IDO or PD-L1 expression. CONCLUSION: Chemotherapy appears to upregulate IDO and PD-L1 expressions in TSCC, highlighting the potential for integrating immunotherapy into treatment regimens. Further studies are needed to explore the dynamics of these biomarkers over time and their impact on patient outcomes, emphasizing the need for comprehensive therapeutic strategies.
背景：舌鳞状细胞癌（TSCC）是一个重大的全球健康问题，发病率和死亡率都很高。目前的治疗方法包括手术、放疗和化疗；然而，预后仍然很差。最近的研究强调了肿瘤微环境，特别是免疫细胞以及PD-L1和IDO等检查点在TSCC进展中的关键作用。 目的：本研究旨在调查TSCC患者化疗前后IDO和PD-L1的表达情况及其与患者临床病理特征的关联。 材料与方法：本研究纳入了巴基斯坦沙卡特汗姆纪念癌症医院及研究中心（SKMCH&RC）的106例TSCC患者，活检样本采集于2012年至2022年。对福尔马林固定、石蜡包埋（FFPE）的肿瘤样本进行免疫组织化学分析，以评估化疗前后IDO和PD-L1的表达。收集患者人口统计学、肿瘤特征和治疗的数据，并持续随访至2024年1月。 结果：该队列的平均年龄为48.9岁，男性患者居多。化疗前，83%的患者IDO呈阴性，75.5%的患者PD-L1呈阴性。化疗后，IDO表达增加至24.5%的患者（n = 26），其中84.6%表现为低表达，15.4%表现为高表达。而PD-L1表达增加至29.2%（n = 31），90.3%的阳性病例表现为低表达，9.7%表现为高表达。IDO表达在多灶性肿瘤中显著更高，且与化疗后合并症增加相关。尽管标志物表达发生了变化，但与IDO或PD-L1表达相关的生存率没有显著差异。 结论：化疗似乎上调了TSCC中IDO和PD-L1的表达，突出了将免疫疗法纳入治疗方案的潜力。需要进一步研究来探索这些生物标志物随时间的动态变化及其对患者预后的影响，强调需要综合治疗策略。
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