Evaluation of PD-1 and interleukin-10-receptor expression by T lymphocytes in malignant and benign pleural effusions.

PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death ligand 1) as well as IL-10 (interleukin-10)/IL-10R (interleukin-10 receptor) interactions play a major role in tumor immune evasion in various malignancies. Several studies investigated the expression of PD-1 on T lymphocytes in pleural effusions (PE) in patients with malignant diseases. However, results in malignant pleural effusions (MPE) compared to benign PE (BPE) are underreported. In this prospective study, 51 patients (median age 66 years, IQR 54-78, 47% male) with PE of malignant or benign origin at the Medical University of Vienna between March 2021 and November 2022 were enrolled and divided into three groups according to the cytological results (group 1: MPE [n = 24, 47%]; group 2: BPE in malignant disease [n = 22, 43%]; group 3: BPE in benign disease [n = 5, 10%]). In the cytological samples, T cells were analyzed for the expression of PD-1 and IL-10R via flow cytometry. In MPE, the proportion of PD-1+ T lymphocytes on CD4+ cells was significantly lower than in BPE (40.1 vs. 56.3 in group 1 vs. 3, p = 0.019). Moreover, a significantly lower expression of PD-1+ IL-10R+ CD8+ (9.6 vs. 35.2 in group 1 vs. 2, p = 0.016; 9.6 vs. 25.0 in group 1 vs. 3, p = 0.032) and a significantly higher expression of PD-1-IL-10R-CD8+ T lymphocytes (43.7 vs. 14.0 in group1 vs. 2, p = 0.045; 43.7 vs. 23.3 in group 1 vs. 3, p = 0.032) were observed in MPE when compared to BPE. The frequency of T cells expressing PD-1 and IL-10R on CD8+ T cells is significantly lower in MPE compared to BPE regardless of the underlying disease indicating a different microenvironment in PE driven by the presence of tumor cells. Our observation spotlights the possible involvement of PD-1 and IL-10R in MPE.

Correlation of PD-L1 expression on tumour cells between diagnostic biopsies and surgical specimens of lung cancer in real life with respect to biopsy techniques and neoadjuvant treatment.

PURPOSES: Programmed death-ligand 1 (PD-L1) testing is performed mainly on biopsy specimens in patients with advanced lung cancer. It is questionable whether the small amount of tissue analysed in biopsies may represent the true PD-L1 expression of a tumour. METHODS: In this retrospective study, PD-L1 expression on tumour cells derived from bronchoscopy brush cytology, endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA), endobronchial biopsy, transbronchial biopsy (TBB) and computed tomography (CT)-guided transthoracic biopsy was compared to the PD-L1 expression of the corresponding surgical resection in lung cancer patients with regard to neoadjuvant treatment in-between. RESULTS: A quantitative comparison between the diagnostic biopsy of the primary tumour with corresponding resected surgical specimens in a total of 113 lung cancer patients (60% male, mean age 65 ± 9 years) revealed a statistically significant correlation of PD-L1 expression on tumour cells (r = 0.58, p< 0.001), for patients without neoadjuvant treatment in-between and for patients who underwent neoadjuvant treatment (both p < 0.001). Using a cut-off value of ≥ 50% PD-L1 TPS for comparing the biopsy samples and resected specimens, the concordance rate was 78% with a Cohen's Kappa of 0.45. CONCLUSION: A statistically significant concordance for PD-L1 expression on tumour cells between biopsies from primary lung tumour and resected specimen was found, but of uncertain clinical accuracy. The use of a cut-off value of ≥ 50% PD-L1 TPS resulted only in a moderate agreement. Therefore, the interpretation of the PD-L1 determined form biopsy specimens status should only be considered with caution for treatment decisionsQuery.