Modifying factors of <scp>PD‐L1</scp> expression on tumor cells in advanced <scp>non‐small‐cell</scp> lung cancer

Avilés‐Salas, Alejandro; Flores‐Estrada, Diana; Lara‐Mejía, Luis; Catalán, Rodrigo; Cruz‐Rico, Graciela; Orozco‐Morales, Mario; Heredia, David; Bolaño‐Guerra, Laura; Pina, Pamela Soberanis; Varela‐Santoyo, Edgar; Cardona, Andrés F.; Arrieta, Óscar

doi:10.1111/1759-7714.14695

Cited by 5 publications

(7 citation statements)

References 33 publications

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“…PD-L1 expression was determined using the VENTANA PD-L1 (SP263) Assay (Ventana Medical Systems, Tucson, AZ, USA) and detected using the OptiView DAB IHC Detection kit on a BenchMark IHC/HIS instrument. SP263 antibody was used as this is the standardized protocol for assessing PD-L1, and it counts with approval from the Food and Drug Administration (FDA) ( 12 ). PD-L1 tumor proportion score (TPS) was calculated as a percentage of at least 100 tumor cells with complete or partial membrane staining.…”

Section: Methodsmentioning

confidence: 99%

PD-L1 expression complements CALGB prognostic scoring system in malignant pleural mesothelioma

Avilés-Salas,

Cabrera-Miranda,

Hernández-Pedro

et al. 2023

Front. Oncol.

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BackgroundProgrammed death ligand-1 (PD-L1) expression is a predictive biomarker in patients with lung cancer, but its role in malignant pleural mesothelioma (MPM) remains unclear. Evidence suggests that higher PD-L1 expression is correlated with worse survival. CALGB is the main scoring system used to predict the benefit of chemotherapy treatment. This study aimed to determine the prognostic value of PD-L1 expression and its addition to CALGB scoring system in patients with MPM.MethodsIn this retrospective analysis, we evaluated samples with confirmed locally advanced or metastatic MPM. PD-L1 Tumor Proportional Score (TPS) was determined by immunohistochemistry at diagnosis.Results73 patients were included in this study. A cutoff value of 15 was set for a high or low PD-L1 TPS. In total, 71.2% (n=52) and 28.8% (n=21) of individuals harbored low or high PD-L1 expression, respectively. PD-L1High was associated with worse median progression-free Survival (mPFS) [4.9 vs. 10.8 months; HR 2.724, 95% CI (1.44-5.14); p = 0.002] and Overall Survival (OS) [6.0 vs. 20.9 months; HR 6.87, 95% CI (3.4-8.7); p<0.001] compared to patients with PD-L1Low. Multivariate analysis confirmed that PD-L1 expression was an independent factor for PFS and OS in patients with MPM and CALGB score of 5-6.ConclusionPD-L1 addition to CALGB scale improves its prognostic estimation of MPM survival and should be considered in future research.

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Section: Methodsmentioning

confidence: 99%

PD-L1 expression complements CALGB prognostic scoring system in malignant pleural mesothelioma

Avilés-Salas,

Cabrera-Miranda,

Hernández-Pedro

et al. 2023

Front. Oncol.

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“…The PD-L1 tumor proportion score (TPS) was calculated as the percentage of at least 100 tumor cells with complete or partial membrane staining. PD-L1 positive samples were de ned using a TPS threshold ≥ 1% [12]. DNA was extracted from para n-embedded tissue sections using the QIAamp DNA FFPE Tissue Kit (Qiagen, Hilden, Germany).…”

Section: Immunohistochemistry Procedures For Cd155 and Pd-l1mentioning

confidence: 99%

Prognostic impact of nectin-like molecule-5 (CD155) expression in Non-Small Cell Lung Cancer

Popa-Navarro,

Avilés-Salas,

Hernández-Pedro

et al. 2024

Preprint

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Objective CD155, a transmembrane protein which inhibits antitumor immune responses, has been shown to be a predictor of worse clinical outcomes in non-small-cell lung cancer (NSCLC). However, its association with the prognosis, clinical and genomic characteristics of Latin American patients remains unexplored. Thus, this study characterizes CD155 expression in NSCLC. Materials and methods Tissue biopsies from 86 consecutive Latin American patients with locally advanced or metastatic NSCLC were assessed for CD155 protein expression, ALK rearrangements and EGFR mutations. Optimal cutoff values for CD155 expression were determined from receiver operating characteristic (ROC) curves according to the 2-year survival of patients with driver and non-driver mutations. Its association with clinicopathological features, median progression-free survival (mPFS), and median overall survival (mOS) was evaluated. Results The cutoff for high CD155 expression (CD155high) was 155 in the entire cohort and in patients without driver mutations, and 110 in patients with driver mutations. CD155 was detected in 84 patients (97.7%), more frequently (52.3%) and at higher levels (62.2%) in patients without driver mutations. EGFR L858R mutation was associated with lower CD155 expression than exon 19 deletion. CD155high patients had a significantly shorter mOS (13.0 vs 30.8 months; HR: 1.96 [95% CI, 1.15–3.35]; p = 0.014). Among patients without driver mutations, CD155high was related to significantly shorter mPFS (1.61 vs 6.40 months; HR: 2.04 [95% CI, 1.03–4.02]; p = 0.034) and mOS (2.92 vs 23.06 months; HR: 2.17 [95% CI, 1.07–4.42]; p = 0.032). In patients with driver mutations, CD155high was only borderline significant for shorter mOS (26.3 vs 52.0 months, HR: 2.39 [95% CI, 0.98–5.83]; p = 0.056). Conclusion CD155high is a predictor of worse survival outcomes in patients with advanced NSCLC, predominantly among those without onco-driver mutations. CD155 could be a potential biomarker and a molecular target in patients with poor responses to current therapies.

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“…[17][18][19] However, validating this hypothesis has proven challenging as most studies investigating the clinicopathological features of NSCLC and PD-L1 expression have primarily focused on patients from North America, Europe, and Asia, while Latin American and African populations have been notably underrepresented. 20,21 Given that there is a significant interest in a better understanding of the role of immunotherapy in oncogenic driven-NSCLC, it becomes crucial to comprehensively assess the factors linked to PD-L1 expression. This understanding could provide valuable insights into the mechanisms underlying primary response or resistance to immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, there is clinical evidence that suggests potential variations in PD‐L1 expression and the effectiveness of immune checkpoint inhibitors based on ethnicity 17–19 . However, validating this hypothesis has proven challenging as most studies investigating the clinicopathological features of NSCLC and PD‐L1 expression have primarily focused on patients from North America, Europe, and Asia, while Latin American and African populations have been notably underrepresented 20,21 …”

Section: Introductionmentioning

confidence: 99%

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Association of PD‐L1 expression with driver gene mutations and clinicopathological characteristics in non‐small cell lung cancer: A real‐world study of 10 441 patients

Ruiz,

Enrico,

Mahmoud

et al. 2024

Thoracic Cancer

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BackgroundProgrammed death ligand‐1 (PD‐L1) expression is a well‐known predictive biomarker of response to immune checkpoint blockade in non‐small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD‐L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America.MethodsThis retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD‐L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples.ResultsA total of 10 441 patients with advanced NSCLC were analyzed. Adenocarcinoma was the most frequent histological subtype (71.1%). PD‐L1 expression was categorized as PD‐L1 negative (45.1%), PD‐L1 positive low‐expression 1%–49% (32.3%), and PD‐L1 positive high‐expression ≥50% (22.6%). Notably, current smokers and males were more likely to have tumors with PD‐L1 tumor proportion score (TPS) ≥50% and ≥ 80% expression, respectively (p < 0.001 and p = 0.013). Tumors with non‐adenocarcinoma histology had a significantly higher median PD‐L1 expression (p < 0.001). Additionally, PD‐L1 in distant nodes was more likely ≥50% (OR 1.60 [95% CI: 1.14–2.25, p < 0.01]). In the multivariate analysis, EGFR‐positive tumors were more commonly associated with PD‐L1 low expression (OR 0.62 [95% CI: 0.51–0.75], p < 0.01), while ALK‐positive tumors had a significant risk of being PD‐L1 positive (OR 1.81 [95% CI: 1.30–2.52], p < 0.01).ConclusionsPD‐L1 expression was associated with well‐defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD‐L1 in patients with advanced NSCLC in a large Latin American cohort.

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Modifying factors of PD‐L1 expression on tumor cells in advanced non‐small‐cell lung cancer

Cited by 5 publications

References 33 publications

PD-L1 expression complements CALGB prognostic scoring system in malignant pleural mesothelioma

PD-L1 expression complements CALGB prognostic scoring system in malignant pleural mesothelioma

Prognostic impact of nectin-like molecule-5 (CD155) expression in Non-Small Cell Lung Cancer

Association of PD‐L1 expression with driver gene mutations and clinicopathological characteristics in non‐small cell lung cancer: A real‐world study of 10 441 patients

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