Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, United States; Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh PA, United States.
Department of Otolaryngology - Head and Neck Surgery, University of Pittsburgh, School of Medicine, Pittsburgh, PA, United States; Department of Acute and Tertiary Care, University of Pittsburgh, School of Nursing, Pittsburgh, PA, United States; Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh PA, United States.
Oral Oncol. 2023 May;140:106363. doi: 10.1016/j.oraloncology.2023.106363. Epub 2023 Mar 22.
Head and neck squamous cell carcinoma (HNSCC) causes severe pain and opioids, the mainstay of pain management, may have immunomodulatory effects. We evaluated the effect of opioids on immunotherapy efficacy in recurrent/metastatic (R/M) HNSCC patients.
In a retrospective study of 66 R/M HNSCC patients from 2015 to 2020, opioid dosage, calculated as mean morphine milligram equivalent per day, was assessed on the day of anti-PD-1 monoclonal antibody (mAb) treatment and most recent prior visit. Intratumoral T cells were evaluated by single cell RNAseq and immunohistochemistry prior to treatment. Univariable and multivariable Cox proportional hazards and logistic regression models were used to estimate the association between opioid usage, progression-free survival (PFS), overall survival (OS), disease control rate.
Patients were 79% male, 35% oropharynx, 35% oral cavity, 40% locoregional recurrence, and 56% platinum failure. Higher opioid dosage by continuous variable was significantly associated with lower PFS (p = 0.016) and OS (p < 0.001). In multivariable analysis, including platinum failure status and PD-L1, higher opioids were associated with lower OS. Opioid usage by categorical variable was associated with significantly lower intratumoral CD8 T cells. Opioid receptor, OPRM1, expression was identified in intratumoral and circulating T cells.
In our study cohort of anti-PD-1 mAb treatment in R/M HNSCC patients, higher opioids were associated with significantly lower PFS and OS and lower CD8 T cells in the tumor microenvironment. To our knowledge, this is the first analysis in R/M HNSCC patients and further research into the clinical and biologic effect of opioids is warranted.
头颈部鳞状细胞癌（HNSCC）可引起严重疼痛，而作为疼痛管理主要手段的阿片类药物可能具有免疫调节作用。我们评估了阿片类药物对复发性/转移性（R/M）HNSCC 患者免疫治疗疗效的影响。
在一项对 2015 年至 2020 年期间 66 例 R/M HNSCC 患者的回顾性研究中，在接受抗 PD-1 单克隆抗体（mAb）治疗当天和最近一次就诊时，评估了阿片类药物的剂量，以每日平均吗啡毫克当量计算。在治疗前通过单细胞 RNAseq 和免疫组织化学评估肿瘤内 T 细胞。使用单变量和多变量 Cox 比例风险和逻辑回归模型来估计阿片类药物使用与无进展生存期（PFS）、总生存期（OS）、疾病控制率之间的关联。
患者中 79%为男性，35%为口咽癌，35%为口腔癌，40%为局部区域复发，56%为铂类耐药。连续变量的阿片类药物剂量越高，PFS（p=0.016）和 OS（p<0.001）越低。多变量分析包括铂类耐药状态和 PD-L1，阿片类药物越高，OS 越低。按分类变量划分的阿片类药物使用与肿瘤内 CD8 T 细胞明显减少相关。在肿瘤内和循环 T 细胞中鉴定到阿片受体 OPRM1 的表达。
在我们的 R/M HNSCC 患者抗 PD-1 mAb 治疗研究队列中，较高的阿片类药物剂量与显著较低的 PFS 和 OS 以及肿瘤微环境中较低的 CD8 T 细胞相关。据我们所知，这是在 R/M HNSCC 患者中进行的首次分析，需要进一步研究阿片类药物的临床和生物学作用。
