Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer

组织微阵列 CD8型 医学 免疫组织化学 PD-L1 宫颈癌 放化疗 危险系数 癌症 病理 预测标记 免疫系统 肿瘤科 免疫疗法 癌症研究 内科学 免疫学 置信区间
作者
Emeka K. Enwere,Elizabeth Kornaga,Michelle L. Dean,Theodora Koulis,Tien Phan,Maria Kalantarian,Martin Köbel,Prafull Ghatage,Anthony M. Magliocco,Susan P. Lees‐Miller,Corinne Doll
出处
期刊:Modern Pathology [Elsevier BV]
卷期号:30 (4): 577-586 被引量:161
标识
DOI:10.1038/modpathol.2016.221
摘要

Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells. We identified 120 patients with locally advanced cervical cancer treated with radical chemoradiotherapy, and built tissue microarrays from their formalin-fixed, paraffin-embedded pre-treatment biopsies. We used conventional brightfield and fluorescence immunohistochemistry to detect PD-L1, and quantified protein expression using both manual pathologist scoring and automated software analysis. We also evaluated the effect of PD-L1 expression in tumors, along with the presence and density of intra-tumoral CD8+ T cells, on patient survival outcomes. Approximately 96% of the tumor samples expressed PD-L1, as determined using quantitative software analysis. Neither expression of PD-L1 nor density of CD8+ T cells was associated with progression-free or overall survival. However, there was a trend towards worse progression-free survival in patients whose tumors expressed PD-L1 but lacked CD8+ T cells (hazard ratio=0.43 (0.18-1.01), P=0.053). Nevertheless, the high percentage of cervical cancer tumor samples expressing PD-L1 suggests that anti-PD-L1 or anti-PD-1 therapies are potential treatment options for this patient population.
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