Relationship of tumor PD-L1 expression withEGFRwild-type status and poor prognosis in lung adenocarcinoma

Abstract

Background: Programmed death-ligand 1 is an immune modulator that promotes immunosuppression by binding to programmed death-1 of T-lymphocytes. Whereas programmed death-ligand 1 expression has been shown to be associated with the clinical response to anti-programmed death-ligand 1 antibody, the association of tumor programmed death-ligand 1 expression with clinicopathological/molecular features and with prognosis remains inconclusive in lung adenocarcinoma. We therefore examined the association of programmed death-ligand 1 expression with the clinicopathological/molecular features and prognosis of lung adenocarcinoma. Methods: Using tissue microarrays of 268 consecutive cases of lung adenocarcinoma, we evaluated programmed death-ligand 1 expression by immunohistochemistry. We examined the association of programmed death-ligand 1 expression with clinicopathological and molecular features. We also examined the prognostic association of programmed death-ligand 1 expression, using the log-rank test as well as Cox proportional hazards regression models to compute the mortality hazard ratio (HR). Results: Programmed death-ligand 1 immunoreactivity (at least 5% of the tumor cells) was observed in 43 (16%) of 268 cases of lung adenocarcinoma. Programmed death-ligand 1 positivity was associated with less tumor differentiation (P < 0.0001) and EGFR wild-type status (P = 0.0008). In a multivariable logistic regression analysis, less tumor differentiation was independently associated with programmed death-ligand 1 positivity (multivariable odds ratio, 6.54; 95% confidence interval [CI], 2.37-23.3; P = 0.0001). Programmed death-ligand 1 positivity was associated with a poor prognosis for lung cancer-specific survival (log-rank, P = 0.019; HR, 1.73; 95% CI, 1.06-2.72; P = 0.030) and overall survival (log-rank, P = 0.0014; HR, 1.88; 95% CI, 1.25-2.74). Conclusion: Our study demonstrated that programmed death-ligand 1 positivity in lung adenocarcinoma was associated with less tumor differentiation and EGFR wild-type status, as well as a poor prognosis.

The correlation between programmed death-ligand 1 expression and driver gene mutations in NSCLC

“…The flow chart of literature searching and the clinical characteristics of included studies were listed in Figure 1 and Table 1, respectively. Of these eligible studies, 5 were from China [17, 18, 20–22], 2 from Japan [16, 19], 2 from Australia [12, 13], 1 from USA [15] and 1 from Italy [14]. The year of publication ranged from 2014 to 2016.…”

“…Among these studies, positive PD-L1 expression appeared in 28.3% of male, 30.3% of female, 36.0% of never smoking, 32.1% of former/current smoking, 28.9% of ADC and 18.6% of non-ADC. Considering the diversity of PD-L1 antibodies, including 4 studies [14, 17, 21, 22] used polyclonal antibodies (PoAbs) and 7 [12, 13, 15, 16, 18–20] utilized monoclonal antibodies (McAbs), we conducted further subgroup analyses based on antibody types (McAbs or PoAbs). The details of PD-L1 antibodies in each study and the cut-off of PD-L1 were listed in Table 2.…”

“…Overall analyses revealed no significant correlation between positive PD-L1 expression and gender (RR = 1.16; 95% CI, 0.95–1.42; P = 0.15, Figure 2A) [12–22]; smoking status (RR = 0.79; 95% CI, 0.56–1.11; P = 0.17, Figure 2B) [12, 16–22]; histological types (RR = 0.94; 95% CI, 0.63–1.41; P = 0.77, Figure 2C) [12–14, 20], respectively. Meanwhile, no significant correlation between positive PD-L1 expression and gender, smoking status, histological types were observed in subgroup analyses on the studies using PD-L1 McAbs (Figure 3), on the studies using PD-L1 PoAbs (Figure 4), on Chinese cohort studies (Figure 5).…”

“…However, considering the fact that obvious heterogeneity existed among these eligible studies ( I 2 = 85%, P < 0.00001), subgroup analyses were conducted based on the studies using PD-L1 McAbs or PoAbs, and on Chinese cohort studies. The outcomes demonstrated that in the studies using PD-L1 McAbs, positive PD-L1 expression more frequently occurred in EGFR mutation group than in wild type group (RR = 0.51; 95% CI, 0.28–0.93; P = 0.03, Figure 6B) [12, 13, 15, 16, 18–20] while the same results were not observed in subgroup analyses on the studies using PD-L1 PoAbs (RR = 1.06; 95% CI, 0.72–1.55; P = 0.77, Figure 6C) [14, 17, 21, 22], and on Chinese cohort studies (RR = 1.08; 95% CI, 0.84–1.38; P = 0.56, Figure 6D) [17, 18, 20–22]. …”

Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation

“…Studies demonstrate that the EGFR activation, by EGF stimulation or mutation, upregulates PD-L1 in lung cancer [19], [37]. However, whether PD-L1 is regulated by the EGFR pathway in ESCC, as well as the regulatory mechanism of the change in PD-L1 expression by chemotherapy, is unexplored.…”