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Tumor PD-L1 status and CD8+ tumor-infiltrating T cells: markers of improved prognosis in oropharyngeal cancer.

ABSTRACT: The aim of this study was to evaluate the expression of PD-L1 in oropharyngeal squamous cell carcinoma. Its relation with clinicopathological variables, tumor infiltrating lymphocytes and survival was also determined.Positive PD-L1 status for the SP142 clone related with improved overall survival in oropharyngeal squamous cell carcinoma. Tumors heavily infiltrated by tumor infiltrating lymphocytes were also linked with better outcome, and this as well for the total number of tumor infiltrating lymphocytes as for the CD3+ and CD8+ T cell count. A Cox proportional hazard model proved that solely infiltrating CD8+ T cells exhibit a positive effect on overall survival (hazard ratio = 0.31 [0.14-0.70]; P = 0.0050).Formalin-fixed, paraffin-embedded tissue from oropharyngeal tumors of 99 patients was immunohistochemically stained for PD-L1 (SP142 and 22C3 clones), CD3, CD8 and FoxP3. Expression of PD-L1, CD3, CD8, FoxP3 and HPV status were correlated with clinicopathological variables. Overall survival was determined by a log-rank (Mantel-Cox) test whereas the Cox proportional hazard model was used for multivariate analysis.Our results demonstrate that CD8+ T lymphocytes constitute an independent prognostic marker in patients diagnosed with oropharyngeal squamous cell carcinoma. PD-L1 positivity for SP142, but not for 22C3, also tends to have a positive effect on survival in oropharyngeal squamous cell carcinoma.

SUBMITTER: De Meulenaere A

PROVIDER: S-EPMC5655210 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Tumor PD-L1 status and CD8<sup>+</sup> tumor-infiltrating T cells: markers of improved prognosis in oropharyngeal cancer.

De Meulenaere Astrid A Vermassen Tijl T Aspeslagh Sandrine S Deron Philippe P Duprez Fréderic F Laukens Debby D Van Dorpe Jo J Ferdinande Liesbeth L Rottey Sylvie S

Oncotarget 20170706 46

<h4>Introduction</h4>The aim of this study was to evaluate the expression of PD-L1 in oropharyngeal squamous cell carcinoma. Its relation with clinicopathological variables, tumor infiltrating lymphocytes and survival was also determined.<h4>Results</h4>Positive PD-L1 status for the SP142 clone related with improved overall survival in oropharyngeal squamous cell carcinoma. Tumors heavily infiltrated by tumor infiltrating lymphocytes were also linked with better outcome, and this as well for the ...[more]

PMID: 29113315

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Project description:BACKGROUND:Brain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features. METHODS:This is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included ?2 test, Cramer's V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation. RESULTS:PD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary tumor PD-L1 expression and the primary tumor type. Significant CD8 peritumoral expression was found in 68.6% of Bmets and in 87.7% of primary tumors. CD8 expression was concordant between primary and metastatic tumors in 73.3% of cases. Bmets CD8 expression was associated with primary tumor CD8 expression and primary tumor type. PD-L1 expression was associated with CD8 expression in both primary and metastatic tumors. The concordance between primary and metastatic tumor PD-L1 expression was independent of all factors studied. The concordance between primary and metastatic CD8 expressions was marginally associated to the time of Bmets development. No prognostic role for PD-L1 and CD8 expression in Bmets was found. CONCLUSION:PD-L1 and CD8 Bmets expressions are associated with the primary tumor type and its PD-L1 and CD8 expressions. No factor predicts the discordance for PD-L1 expression, while time to Bmets development is associated with CD8 expression discordance.

Project description:Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms that are composed of myofibroblastic cells accompanied by inflammatory infiltrate. We investigated the immune profiles of IMTs, including PD-L1 expression and proportion of CD8+ tumor-infiltrating lymphocytes (TILs), as well as its clinicopathological characteristics according to ALK gene rearrangementstatus.Twenty-eight IMTs from 25 patients were retrieved from our pathology files (2005-2015), and their clinicopathological parameters and outcomes were analyzed. Immunohistochemistry (IHC) was performed using whole-tissue sections to detect PD-L1 and CD8 expression, and fluorescent in situ hybridization (FISH) analysis and IHC were performed using tissue microarrays to identify rearrangements in the ALK, ROS1, and RET genes.ALK rearrangement was observed in 11 cases (44.0%), and all cases exhibited diffuse cytoplasmic ALK expression during IHC. ROS1 or RET rearrangement was not detected using IHC or FISH. IMTs harboring ALK rearrangement (ALK-positive) were located in the lungs (n = 7), genitourinary tract (n = 2), and mesentery (n = 1). The mean patient age was 33.2 years for ALK-positive IMTs and 53.1 years for ALK-negative IMTs. All patients with ALK-positive IMTs survived without recurrence or metastasis. IMTs with metastasis and/or recurrence were ALK-negative and exhibited elevated PD-L1 expression (positive tumor cells: 70.0% vs. 21.3%, P = 0.023; H-score: 107.5 vs. 26.3, P = 0.005). In addition, ALK-negative IMTs had a more CD8+ TILs, compared to ALK-positive IMTs (23.3% vs. 8.9%, P = 0.027).ALK-positive IMTs are characterized by younger age, well-defined margins, frequent involvement of the lung, and fewer CD8+ TILs. Greater PD-L1 expression was observed in IMTs with tumor necrosis and metastasis/recurrence, which were also negative for ALK rearrangement. These results suggest that immune checkpoint inhibitors may be a novel option for treating patients with advanced IMT.

Dataset Information

Tumor PD-L1 status and CD8+ tumor-infiltrating T cells: markers of improved prognosis in oropharyngeal cancer.

Publications

Tumor PD-L1 status and CD8<sup>+</sup> tumor-infiltrating T cells: markers of improved prognosis in oropharyngeal cancer.

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