Background: Although small cell lung carcinomas (SCLC) show an initial response to treatment, patients rapidly suffer disease recurrence and become refractory to chemotherapy. Despite intensive research, the prognosis of SCLC remains poor, and therefore new strategies to improve outcome are urgently needed. Blockade of immune checkpoints PD-1/PD-L1 with monoclonal antibodies has recently emerged as a new therapeutic tool in oncology. Due to the difficulty in obtaining adequate tissue in diseases such as SCLC for PD-L1 expression assessment, we investigated the usefulness of circulating tumor cells (CTCs) detection as a non-invasive method to evaluate PD-L1 status in SCLC patients.
Materials and Methods: CTC capture and PD-L1 expression was evaluated in a cohort of 18 SCLC patients for whom resected tissue specimens were available and were positive for CTCs, as detected by using the filtration-based ISET platform (Rarecells Diagnostics, Paris, France). PD-L1 expression was evaluated in ISET-captured CTCs and FFPE tissue sections by immunohistochemistry (IHC) using the SP142 rabbit monoclonal antibody (Spring Bioscience, USA). PD-L1 expression was scored on tumor cells (TC3≥50% positive tumor cells; TC2≥5% but <50% positive tumor cells; TC1≥1% but <5% of positive tumor cells; and TC0<1% positive tumor cells) and tumor-infiltrating immune cells (IC3≥10% of positive immune cells; IC2≥5% but <10% of positive immune cells; IC1≥ 1% but <5% of positive immune cells; and IC0< 1% of positive immune cells).
Results: None of the SCLC cases showed PD-L1 protein expression in tumor cells on tissue specimens. PD-L1 expression was observed in the stroma. Using IHC assay, 67% of cases (8/12) were scored IC1-3 based on PD-L1 expression in tumor-infiltrating immune cells and 42% (5/12) were scored IC2/3. On the ISET platform, CTCs enumeration ranged from 3 to 637 CTCs/6 ml, with median 11 CTCs/6 ml, and clusters of CTCs in 83% of patients. No PD-L1 expression was observed in CTCs. However, 42% of cases showed PD-L1 expression in circulating immune cells, with PD-L1 status on filters being concordant with the IC2/3 status in patient-matched tumor tissue.
Conclusion: PD-L1 seems expressed in only a fraction of SCLC, with carcinoma cells being negative in all cases, and PD-L1 expressed in tumor-infiltrating immune cells. Patients with stromal PD-L1 expression may potentially respond to anti-PD-1 treatment. Besides conventional IHC, ISET platform seems suitable for non-invasive real-time detection of circulating PD-L1 expression to determine PD-L1 status of SCLC patients entering clinical trials.
Citation Format: Marius Ilie, Véronique Hofman, Elodie Long, Catherine Butori, Salomé Lalvée, Eric Selva, Nicolas Vénissac, Jérôme Mouroux, Charles Hugo Marquette, Paul Hofman. PD-L1 expression in primary tumor and circulating tumor cells in patients with small cell lung carcinomas. [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 2220.