High levels of PD-L1 on platelets of NSCLC patients contributes to the pharmacological activity of Atezolizumab

Colarusso, Chiara; Falanga, Anna; Terlizzi, Michela; De Rosa, Ilaria; Somma, Pasquale; Sommella, Eduardo Maria; Caponigro, Vichy; Panico, Luigi; Salviati, Emanuela; Campiglia, Pietro; Salatiello, Giuseppe; Tramontano, Teresa; Maiolino, Piera; Pinto, Aldo; Sorrentino, Rosalinda

doi:10.1016/j.biopha.2023.115709

Cited by 3 publications

(2 citation statements)

References 20 publications

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“…There has been growing interest in exploring the potential predictive value of PD-L1 expression on PLTs in the context of response to PD-(L)1 inhibitors. In line with our findings, Colarusso et al demonstrated that increased PD-L1 expression in PLTs correlated with a longer clinical benefit from anti-PD-L1 therapy in NSCLC patients [39]. Some studies have pointed to the transfer of PD-L1 protein from tumor cells to blood PLTs during their interaction in a fibronectin-and integrin α5β1-dependent manner [24].…”

Section: Discussionsupporting

confidence: 89%

Potential Role of Circulating PD-L1+ Leukocytes as a Predictor of Response to Anti-PD-(L)1 Therapy in NSCLC Patients

Anguera,

Mulet,

Zamora

et al. 2024

Biomedicines

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PD-(L)1 inhibitors are part of the treatment strategy for non-small cell lung cancer (NSCLC) although its efficacy is limited to certain patients. Our study aimed to identify patients who might benefit from anti-PD-(L)1 inhibitors by analyzing the PD-L1 expression on circulating leukocytes and its evolution during treatment. One hundred thirteen NSCLC patients, according to their radiological response after 10–12 weeks of treatment, were classified into responders, stable, and progressive disease. Percentages of circulating PD-L1+ leukocytes, PD-L1+ platelets (PLTs), and leukocyte-PLT complexes were assessed using flow cytometry, and plasma concentrations of soluble immunomodulatory factors were quantified by ELISA. Responders exhibited significantly higher pre-treatment percentages of PD-L1+ neutrophils, PD-L1+ CD14+ cells, and PD-L1+ PLTs than progressors. The percentages of these populations decreased in responders post-treatment, contrasting with stables and progressors. PLTs notably contributed to PD-L1 expression in CD14+ cells and neutrophils. Plasma cytokine analysis revealed baseline differences only in IL-17 concentration among groups, whereas network analyses highlighted distinct association patterns between plasma molecules and PD-L1+ leukocytes after 10–12 weeks of treatment. Our findings suggest that pre-treatment assessment of circulating PD-L1+ neutrophils, PD-L1+ CD14+ cells, and PD-L1+ PLTs may be helpful in identifying NSCLC patients who are potential candidates for anti-PD-(L)1 therapy.

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Section: Discussionsupporting

confidence: 89%

Potential Role of Circulating PD-L1+ Leukocytes as a Predictor of Response to Anti-PD-(L)1 Therapy in NSCLC Patients

Anguera,

Mulet,

Zamora

et al. 2024

Biomedicines

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“…One study reported that PD-L1 mRNA expression in plasma-derived exosomes could help predict the clinical responses of melanoma or NSCLC patients who received anti-PD-1 therapy ( 28 ). Colarusso et al reported that PD-L1 on platelets represent an easy-to-use clinical approach to predict ICI responsiveness ( 29 ). Taken together, the predictive value of TEP PD-L1 in immunotherapy is supported by its biological process and related research findings (including those of the present study).…”

Section: Discussionmentioning

confidence: 99%

PD-L1 mRNA derived from tumor-educated platelets as a potential immunotherapy biomarker in non-small cell lung cancer

Hu,

Wang,

Zhang

et al. 2024

Transl Lung Cancer Res

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Background To date, the role of programmed death ligand-1 (PD-L1) messenger RNA (mRNA) derived from tumor-educated platelets (TEPs) has not been well investigated in patients with advanced non-small cell lung cancer (NSCLC). A few reports have examined whether mRNA in TEPs can predict the clinical responses of patients with advanced NSCLC following immunotherapy. This study aimed to identify novel biomarkers to improve the clinical benefits and outcomes of NSCLC patients. Methods Advanced NSCLC patients receiving a combination of immunotherapy and chemotherapy, or immunotherapy alone as a first- or second-line treatment at the Fudan University Shanghai Cancer Center were enrolled in this study. All the patients had wild-type epidermal growth factor receptor/anaplastic lymphoma kinase. The patients were enrolled in clinical trials for immune checkpoint inhibitors (ICIs), including nivolumab, pembrolizumab, atezolizumab, durvalumab, tremelimumab, and camrelizumab. Tumoral PD-L1 expression was tested by immunohistochemistry (PD-L1 22C3 pharmDx kit, Agilent, Santa Clara, CA, USA) in archived tissue samples, when available, to calculate the tumor proportion scores (TPSs). RNA and exosomal RNA of blood were isolated before immunotherapy using the Yunying RNA extraction kit (Yunying Medicine, Shanghai, China). The concentration and quality of the RNA was determined using a Qubit fluorometer (Life Technologies, Carlsbad, CA, USA). Finally, we analyzed the predictive value of TEP-derived PD-L1 mRNA expression and association with the level of the tumoral PD-L1 expression. Results In total, 72 patients were enrolled in this study. Most of the patients were male (n=54, 75.0%), had adenocarcinoma (n=49, 68.1%). We found there was no significant correlation between the TEP-derived mRNA of PD-L1 and tumoral PD-L1 expression based on the results of the Pearson Correlation test (r=−0.19, P=0.233). Based on the median of PD-L1 mRNA, 72 patients were divided into a high PD-L1 group and a low PD-L1 group. We found that 19 patients (44.4%) responded to immunotherapy [partial response or progression-free survival (PFS) >6 months] in the high PD-L1 group, but only five patients (13.9%) responded to immunotherapy in the low PD-L1 group (P<0.01). The median PFS of the low PD-L1 group was lower than that of the high PD-L1 group (2.8 vs. 8.3 months, P<0.001). For the patients who were treated with immunotherapy alone (n=64), a similar PFS advantage was observed in the high PD-L1 group (2.8 vs. 8.0 months, P=0.002). Conclusions This article presented the first data on TEP-derived PD-L1 mRNA in advanced NSCLC patients following immunotherapy and showed the potential advantage of using it as the surrogate biomarker for predicting the PFS and overall survival of patients following immunotherapy.

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The Importance of Predictive Biomarkers and Their Correlation with the Response to Immunotherapy in Solid Tumors—Impact on Clinical Practice

Mihaila,

Gheorghe,

Zob

et al. 2024

Biomedicines

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Background/Objectives: Immunotherapy has changed the therapeutic approach for various solid tumors, especially lung tumors, malignant melanoma, renal and urogenital carcinomas, demonstrating significant antitumor activity, with tolerable safety profiles and durable responses. However, not all patients benefit from immunotherapy, underscoring the need for predictive biomarkers that can identify those most likely to respond to treatment. Methods: The integration of predictive biomarkers into clinical practice for immune checkpoint inhibitors (ICI) holds great promise for personalized cancer treatment. Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), microsatellite instability (MSI), gene expression profiles and circulating tumor DNA (ctDNA) have shown potential in predicting ICI responses across various cancers. Results: Challenges such as standardization, validation, regulatory approval, and cost-effectiveness must be addressed to realize their full potential. Predictive biomarkers are crucial for optimizing the clinical use of ICIs in cancer therapy. Conclusions: While significant progress has been made, further research and collaboration among clinicians, researchers, and regulatory institutes are essential to overcome the challenges of clinical implementation. However, little is known about the relationship between local and systemic immune responses and the correlation with response to oncological therapies and patient survival.

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High levels of PD-L1 on platelets of NSCLC patients contributes to the pharmacological activity of Atezolizumab

Cited by 3 publications

References 20 publications

Potential Role of Circulating PD-L1+ Leukocytes as a Predictor of Response to Anti-PD-(L)1 Therapy in NSCLC Patients

Potential Role of Circulating PD-L1+ Leukocytes as a Predictor of Response to Anti-PD-(L)1 Therapy in NSCLC Patients

PD-L1 mRNA derived from tumor-educated platelets as a potential immunotherapy biomarker in non-small cell lung cancer

The Importance of Predictive Biomarkers and Their Correlation with the Response to Immunotherapy in Solid Tumors—Impact on Clinical Practice

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