Association between PD‐L1 expression and initial brain metastasis in patients with non‐small cell lung cancer and its clinical implications

Abstract

Background: Brain metastases frequently occur in patients with non-small cell lung cancer (NSCLC) resulting in a poor prognosis. Here, we investigated the association between PD-L1 expression and brain metastasis in patients with NSCLC and its clinical significance. Methods: A total of 270 patients diagnosed with metastatic NSCLC who underwent PD-L1 testing on their tumor tissue between January 2017 and March 2019 were retrospectively reviewed. The VENTANA PD-L1 (SP263) assay was used, and positive PD-L1 expression was defined as staining in ≥1% of tumor cells. Results: Positive PD-L1 expression was observed in 181 (67.0%) patients, and 74 (27.4%) patients had brain metastasis at diagnosis. Synchronous brain metastases were more frequently observed in PD-L1-positive compared with PD-L1-negative patients (31.5% vs. 19.1%, p = 0.045). Multiple logistic regression analysis identified positive PD-L1 expression (odds ratio [OR]: 2.24, p = 0.012) as an independent factor associated with synchronous brain metastasis, along with the histological subtype of nonsquamous cell carcinoma (OR: 2.84, p = 0.003). However, the incidence of central nervous system (CNS) progression was not associated with PD-L1 positivity, with a two-year cumulative CNS progression rate of 26.3% and 28.4% in PD-L1-positive and PD-L1-negative patients, respectively (log rank p = 0.944). Furthermore, positive PD-L1 expression did not affect CNS progression or overall survival in patients with synchronous brain metastasis (long rank p = 0.513 and 0.592, respectively). Conclusions: Initial brain metastases are common in NSCLC patients with positive PD-L1 expression. Further studies are necessary to understand the relationship between early brain metastasis and cancer immunity.

Spatial and temporal heterogeneity of tumor immune microenvironment between primary tumor and brain metastases in NSCLC

“…We found that in brain metastasis tissue, PD-L1 positivity was more common in synchronous metastases than in metachronous metastases. This is similar to the findings of Lee et al, who performed IHC of PD-L1 on primary lung cancer tissues of 270 patients with NSCLC brain metastases, and the results showed that compared with PD-L1-negative patients, synchronous brain metastases were more frequently observed in PD-L1-positive patients [ 40 ]. This indicates that PD-L1 expression is strongly correlated with synchronous metastasis whether detected in primary lung tumors or brain metastases.…”

Combined Assessment of Preoperative Frailty and Sarcopenia Allows the Prediction of Overall Survival in Patients with Lung Cancer (NSCLC) and Surgically Treated Brain Metastasis

“…Nevertheless, several studies have revealed a reduced OS in patients with sarcopenia despite treatment with immune checkpoint inhibitors [29,30]. In addition, positive PD-L1 expression was reported more frequently in patients with primary brain metastases [31]. In the present patient population, the analysis of PD-L1 expression could only be performed in 22%.…”

Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology

“…FASN-driven PD-L1 palmitoylation may provide a novel mechanism by which metastatic cancer cells can overcome the innate and adaptive immune responses to enable brain metastasis colonization. This is due to the high concordance between primary and brain metastatic tumor PD-L1 expression [356] and the association of PD-L1 expression with early brain metastasis [357]. The potential role of FASN in dynamically regulating the palmitoylated or depalmitoylated state of CD36, which is known to abolish its FA uptake activity, deserves further analysis to provide a more complete understanding of FASN-regulated palmitoylation as a preventive target for brain metastasis in combination with PD-1/PD-L1 blockade.…”