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

被引:138
|
作者
Enwere, Emeka K. [1 ]
Kornaga, Elizabeth N. [1 ]
Dean, Michelle [1 ]
Koulis, Theodora A. [2 ]
Tien Phan [2 ]
Kalantarian, Maria [1 ]
Kobel, Martin [3 ]
Ghatage, Prafull [2 ]
Magliocco, Anthony M. [4 ]
Lees-Miller, Susan P. [5 ]
Doll, Corinne M. [2 ]
机构
[1] Tom Baker Canc Clin, Translat Labs, Calgary, AB, Canada
[2] Tom Baker Canc Clin, Dept Oncol, 1331 29th St NW, Calgary, AB T2N 4N2, Canada
[3] Calgary Lab Serv, Dept Pathol & Lab Med, Calgary, AB, Canada
[4] H Lee Moffitt Canc Ctr & Res Inst, Dept Anat Pathol, Tampa, FL USA
[5] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada
关键词
TUMOR-INFILTRATING LYMPHOCYTES; NEGATIVE BREAST-CANCER; LUNG-CANCER; ANTI-PD-L1; ANTIBODY; IMMUNE CHECKPOINT; CLINICAL ACTIVITY; OPEN-LABEL; CARCINOMA; MULTICENTER; HEAD;
D O I
10.1038/modpathol.2016.221
中图分类号
R36 [病理学];
学科分类号
100104 ;
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.
引用
收藏
页码:577 / 586
页数:10
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