Abstract 2218: Distribution and prognostic relevance of PD-1/PD-L1 immune checkpoints and tumor-infiltrating lymphocytes in early-stage pulmonary basaloid squamous cell carcinoma
Authors: Ilie Marius , Butori Catherine , Hofman Véronique , Bonnetaud Christelle , Lassalle Sandra , Long Elodie , Lalvée Salomé , Vénissac Nicolas , Mouroux Jérôme , Marquette Charles Hugo , Hofman Paul 
Published: July 2016

Background: The activation of immune cells by immune checkpoint inhibitors showed promising results with increased patient survival in several types of cancer. Since no data exist for pulmonary basaloid squamous cell carcinoma (BSCC), we aimed to characterize the expression of PD-L1 and PD-1 as well as tumor infiltrating lymphocytes (TILs) in operable BSCC.

Materials and Methods: We retrospectively included 57 patients with operable stages I-III BSCC. The expression of PD-L1 (clone SP142, Spring Bioscience), PD-1 (clone NAT105, Ventana) and CD8 (clone SP57, Ventana) was evaluated by automated immunohistochemical analysis in FFPE specimens of BSCC. PD-L1 expression was scored on tumor cells (TC3≥50% positive tumor cells; TC2≥5% but &lt;50% positive tumor cells; TC1≥1% but &lt;5% of positive tumor cells; and TC0&lt;1% positive tumor cells) and tumor-infiltrating immune cells (IC3≥10% of positive immune cells; IC2≥5% but &lt;10% of positive immune cells; IC1≥ 1% but &lt;5% of positive immune cells; and IC0&lt; 1% of positive immune cells). Survival analysis was determined by Kaplan-Meier analysis and Cox proportional hazard models.

Results: PD-L1 expression on tumor cells (TC1-3) was observed in 30% of patients (17/57), with high-PD-L1 expressing TC (TC2/3) in 14% of cases (8/57). PD-L1 expression on tumor-infiltrating immune cells was noticed in 36% of patients (20/57), with high-PD-L1 expressing IC (IC2/3) in 18% of cases (10/57). PD-L1 expression strongly correlated with CD8+ TILs and PD-1+ expression. CD8+ TILs infiltrated the tumors in three different patterns (stromal, peritumoral, diffuse). High PD-L1 expression either on TC or IC was significantly associated with better progression-free survival (PFS) (TC0, P = 0.024; TC0/IC0, P = 0.03) and overall survival (OS) (TC0, P = 0.01; TC0/IC0, P = 0.007) in BSCC patients. High amounts of TILs and PD-1+ cells were significantly correlated with improved PFS (TILs, P = 0.035; PD-1+, P = 0.007) and OS (TILs, P = 0.016; PD-1+, P = 0.03).

Conclusion: Increased PD-L1 TC and IC levels, TILs density and PD-1+ infiltrates are associated with better outcome in early-stage BSCC. Assessment of PD-L1 expression along with PD-1+ and CD8+ TILs could be useful to predict response to immune checkpoint inhibitors in BSCC. [M.I. and C.B. contributed equally to this work.]

Citation Format: Marius Ilie, Catherine Butori, Véronique Hofman, Christelle Bonnetaud, Sandra Lassalle, Elodie Long, Salomé Lalvée, Nicolas Vénissac, Jérôme Mouroux, Charles Hugo Marquette, Paul Hofman. Distribution and prognostic relevance of PD-1/PD-L1 immune checkpoints and tumor-infiltrating lymphocytes in early-stage pulmonary basaloid squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2218.