Differential Expression of PD-L1 in Central and Peripheral and TTF1-Positive and -Negative Small-Cell Lung Cancer

Abstract

Background: Central and peripheral location as well as thyroid transcription factor-I (TTF-1) expression was reported to be associated with different characteristics and prognosis of small-cell lung cancer (SCLC). This study aimed to investigate differential expression of PD-L1 in different SCLC subtypes, and in biopsy and resection specimens.Methods: We retrospectively analyzed 142 SCLC tumor samples using immunohistochemistry to correlate PD-L1 (22C3) expression with clinicopathologic features and survival data.Results: PD-L1 expression was found in 19.7% SCLCs (28/142) and was more frequent in females than in males (32%, 16/50 vs. 13%, 12/92, p = 0.009), in central type than in peripheral type SCLCs (26%, 26/100 vs. 4.8%, 2/42, p = 0.003), and in TTF-1 positive than in negative SCLCs (23.8%, 25/105 vs. 8.1%, 3/37, p = 0.039). PD-L1 expression was associated with vascular (p = 0.001) and lymphatic invasion (p = 0.001). There was no significant difference in PD-L1 expression between biopsy and resection specimens. On univariate analysis, patients with PD-L1 expression had significantly shorter progression-free survival (PFS; p = 0.026) and overall survival (OS; p = 0.012). Multivariate analysis revealed that PD-L1 expression was an independent prognostic factor for OS (HR, 2.317; 95% CI 1.199–4.478; p = 0.012) and PFS (HR, 1.636; 95% CI 0.990–2.703; p = 0.051) in SCLC.Conclusions: PD-L1 expression was more frequent in central type, TTF-1 positive SCLCs, and predicted a poor clinical outcome in these patients. Therefore, tumor location and TTF-1 expression could predict expression status of PD-L1, and could potentially serve as clinical response to immunotherapy.

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

“…Yu and colleagues reported similar numbers for a cohort of 142 SCLC patients with >1% staining positivity in 19.7% of cases. Of note, tumor-associated lymphocytes and macrophages that stained >1% for PD-L1 expression were reported in even greater numbers in 41.5% of cases [ 66 ]. In the recent study where pembrolizumab monotherapy did not improve progression-free survival, except in the sub-group of SCLC patients with high PD-L1 expression at the stromal interface, only 1 PD-L1+ case out of 35 was found when using DAKO 22C3, which was assessed on tumor cells [ 52 ].…”

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis

“…The study revealed a higher prevalence of PD-L1 expression in centrally located SCLC cases exhibiting positive TTF-1 expression. The findings suggest that PD-L1 expression serves as an unfavorable prognostic factor in SCLC, particularly when associated with vascular and lymphatic infiltration [ 45 ]. In this investigation, the majority of specimens derived from 18 cases of SCLC demonstrated a negative expression of PD-L1 in tumor cells.…”

Promises of Protein Kinase Inhibitors in Recalcitrant Small-Cell Lung Cancer: Recent Scenario and Future Possibilities

“…The inhibition of PD-L1 (programmed cell death ligand 1 (or CD274)/PD-1 (programmed cell death 1) (or CD279) signaling has demonstrated potential in the therapeutic approach to ES-SCLC by augmenting tumor-specific T-cell immunity [ 10 , 11 , 12 , 13 ]. In the context of SCLC, it has been observed that PD-L1 is expressed in different cellular compartments of SCLC tissues, including NE marker-positive tumor cells [ 55 , 56 ]. The anti-PD-L1 antibody Atezolizumab was first evaluated in combination with carboplatin–etoposide chemotherapy in a phase III IMpower 133 clinical trial (NCT02763579) [ 10 , 11 , 12 , 13 ].…”