Circulating leukocyte–platelet complexes as a predictive biomarker for the development of immune-related adverse events in advanced non-small cell lung cancer patients receiving anti-PD-(L)1 blocking agents

Zamora, Carlos; Riudavets, Mariona; Anguera, Geòrgia; Alserawan, Leticia; Sullivan, Ivana; Barba, Andrés; Serra, J.P.C.; Ortiz, M; Gallardo, Pablo; Perea, Lídia; Gavira, J.; Barnadas, Agustí; Majem, Margarita; Vidal, Sílvia

doi:10.1007/s00262-020-02793-4

Cited by 10 publications

(4 citation statements)

References 47 publications

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“…We found that the mCRPC patients had a higher percentage of monocyte–platelet complexes than the HDs. Other authors have reported higher percentages of these complexes in lung cancer patients [ 26 ], but this is the first description for mCRPC patients. There is known to be a close relationship between platelets and cancer, probably because tumor cells can activate platelets [ 27 ].…”

Section: Discussionmentioning

confidence: 73%

Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomes of Radium-223 Treatment

et al. 2023

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(1) Background: Prostate cancer is the second most common cancer in men, with androgen suppression as the standard treatment. Despite initially responding to castration, most metastatic prostate cancer patients eventually experience progression. In these cases, Radium-223 is the chosen treatment. We hypothesized that the immunophenotype of circulating leukocytes conditions the response to Radium-223 treatment. (2) Material and Methods: In this prospective study, we collected peripheral blood from twelve mCRPC patients and nine healthy donors before (baseline) and during treatment with Radium-223. Immunophenotyping and the percentages of leukocyte–platelet complexes were determined by flow cytometry. The increments or decrements of leukocyte subsets between the baseline and the second Radium-223 injection were also calculated. (3) Results: At baseline, the mCRPC patients had a lower percentages of CD4+ T cells and B cells and higher percentages of NK and neutrophils than the HDs. In addition, they had more OX40+ CD4+ T cells, PD-L1+ CD8low cells, PD-L1+ B cells, PD-L1+ NK cells, and monocyte–platelet complexes than the HDs. Moreover, patients with slow and fast progression had different percentages of PD-L1+ CD8+ T cells. In particular, slow progression patients underwent an increment of PD-L1+ CD8+ T cells after two cycles of Radium-223. (4) Conclusions: The characterization of circulating immune cells before initiating Radium-223 treatment could become a non-invasive indicator of the response.

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Section: Discussionmentioning

confidence: 73%

Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomes of Radium-223 Treatment

et al. 2023

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“…Through both direct and indirect interactions with leukocytes, PLTs regulate several aspects of tumor-associated pathology, including tumor growth and metastasis. In a previous publication, we demonstrated that patients with NSCLC exhibit higher percentages of circulating leukocyte-PLT complexes compared to HD and, particularly, complexes of CD4 + T cell-PLTs and CD14 + cell-PLTs can be used as a predictive biomarker of the development and severity of immune-related adverse events associated to ICI therapy [22]. Recent reports also indicate that PLTs may increase PD-L1 expression in cancer conditions, potentially attenuating the antitumor immune response [23].…”

Section: Introductionmentioning

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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“…Platelet binding and release of cytokines and growth factors like TGF-βdecrease T cell proliferation and production of inflammatory cytokines hence promoting immunoregulatory effect. Notably, platelet-monocyte complex was found to be higher in patients with systemic inflammation and Acquired Immunodeficiency Disease (AID) [79]. A similar study that used single RNA sequencing to identify immune cell types and biomarkers associated with irAEs, found that irAEs were associated with acute increase in monocytes and decrease in T cells [80].…”

Section: The Role Of Platelets In Immunity Inflammation and Iraesmentioning

confidence: 99%

The Potential Role of Circulating Inflammatory Cells in Predicting the Safety, Efficacy and Immune-related Adverse Events of Immune Check-point Inhibitors: A Narrative Review

K Rugambwa

2023

GMR

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Immune checkpoint blockade has influenced the course of cancer treatment with improved Overall Survival (OS) and durable responses in many malignancies. Despite these responses, their mechanism of action has brought different set of adverse events that are severe and life-threatening in a subset of patients. Moreover, not all patients have shown to benefit from this treatment although their tumors express U.S. Federal and Drug Administration (FDA) approved biomarkers i.e programmed cell Death Protein 1 (PD-1) and its ligand (PD-L1), Microsatellite Instability (MSI) and Tumor Mutation Burden (TMB). Limitations of these markers has stimulated further research to identify and incorporate other markers that could serve as an adjunct to the current approved ones. Circulating inflammatory cells are among biomarkers that have shown to have a prognostic and predictive value in determining treatment response to Immune Checkpoint Inhibitors (ICI) and risk of Immune-Related Adverse Events (irAEs). This review aims to provide more details on the key inflammatory cells that play a pivotal role in cancer progression and inhibition and how their interaction in the tumor micro-environment (TME) affects response to immune checkpoint blockade and predicting irAEs. Moreover examples of prognostic models that have incorporated these cells will be highlighted.

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Circulating leukocyte–platelet complexes as a predictive biomarker for the development of immune-related adverse events in advanced non-small cell lung cancer patients receiving anti-PD-(L)1 blocking agents

Cited by 10 publications

References 47 publications

Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomes of Radium-223 Treatment

Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomes of Radium-223 Treatment

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

The Potential Role of Circulating Inflammatory Cells in Predicting the Safety, Efficacy and Immune-related Adverse Events of Immune Check-point Inhibitors: A Narrative Review

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