title: Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer.
abstract: 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.
authors.affiliation: Translational Laboratories, Tom Baker Cancer Centre, Calgary, AB, Canada.
authors.forename: Emeka K
authors.initials: EK
authors.lastname: Enwere
authors.affiliation: Translational Laboratories, Tom Baker Cancer Centre, Calgary, AB, Canada.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Kornaga
authors.affiliation: Translational Laboratories, Tom Baker Cancer Centre, Calgary, AB, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Dean
authors.affiliation: Department of Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada.
authors.forename: Theodora A
authors.initials: TA
authors.lastname: Koulis
authors.affiliation: Department of Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada.
authors.forename: Tien
authors.initials: T
authors.lastname: Phan
authors.affiliation: Translational Laboratories, Tom Baker Cancer Centre, Calgary, AB, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Kalantarian
authors.affiliation: Department of Pathology and Laboratory Medicine, Calgary Laboratory Services, Calgary, AB, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.affiliation: Department of Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada.
authors.forename: Prafull
authors.initials: P
authors.lastname: Ghatage
authors.affiliation: Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Magliocco
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Lees-Miller
authors.affiliation: Department of Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada.
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Doll
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D060890:B7-H1 Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002584:Cervix Uteri / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human