Circulating innate immune markers and outcomes in treatment-naïve advanced non–small cell lung cancer patients

Charrier, Mélinda; Mezquita, Laura; Lueza, Béranger; Dupraz, Louise; Planchard, David; Remón, Jordi; Caramella, Caroline; Cassard, Lydie; Boselli, Lisa; Reiners, Katrin S.; Strandmann, Elke Pogge von; Rusakiewicz, Sylvie; Ferrara, Roberto; Duchemann, Boris; Naigeon, Marie; Pignon, Jean‐Pierre; Besse, Benjamin; Chaput, Nathalie

doi:10.1016/j.ejca.2018.12.017

Cited by 35 publications

(24 citation statements)

References 33 publications

(40 reference statements)

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“…Recently, we demonstrated that the levels of NCR3/NKp30 transcripts were independently associated with the outcomes in treatment-naive patients with advanced NSCLC. 48 These observations are critical and promising for the activity of RLI in clinic. NK cells play an important role in immunosurveillance of cancer with the ability to kill tumor cells escaping T cell recognition through the down-regulation of MHC-I for instance.…”

Section: Discussionmentioning

confidence: 89%

IL-15 superagonist RLI has potent immunostimulatory properties on NK cells: implications for antimetastatic treatment

Desbois

Béal

Charrier

et al. 2020

J Immunother Cancer

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BackgroundAs the immune system is compromised in patients with cancer, therapeutic strategies to stimulate immunity appear promising, to avoid relapse and increase long-term overall survival. Interleukin-15 (IL-15) has similar properties to IL-2, but does not cause activation-induced cell death nor activation and proliferation of regulatory T cells (Treg), which makes it a serious candidate for anticancer immunotherapy. However, IL-15 has a short half-life and high doses are needed to achieve responses. Designed to enhance its activity, receptor-linker-IL-15 (RLI) (SO-C101) is a fusion molecule of human IL-15 covalently linked to the human IL-15Rα sushi+ domain currently assessed in a phase I/Ib clinical trial on patients with advanced/metastatic solid cancer.MethodsWe investigated the antimetastatic activity of RLI in a 4T1 mouse mammary carcinoma that spontaneously metastasizes and evaluated its immunomodulatory role in the metastatic lung microenvironment. We further characterized the proliferation, maturation and cytotoxic functions of natural killer (NK) cells in tumor-free mice treated with RLI. Finally, we explored the effect of RLI on human NK cells from healthy donors and patients with non-small cell lung cancer (NSCLC).ResultsRLI treatment displayed antimetastatic properties in the 4T1 mouse model. By characterizing the lung microenvironment, we observed that RLI restored the balance between NK cells and neutrophils (CD11b+Ly6GhighLy6Clow) that massively infiltrate lungs of 4T1-tumor bearing mice. In addition, the ratio between NK cells and Treg was strongly increased by RLI treatment. Further pharmacodynamic studies in tumor-free mice revealed superior proliferative and cytotoxic functions on NK cells after RLI treatment compared with IL-15 alone. Characterization of the maturation stage of NK cells demonstrated that RLI favored accumulation of CD11b+CD27highKLRG1+mature NK cells. Finally, RLI demonstrated potent immunostimulatory properties on human NK cells by inducing proliferation and activation of NK cells from healthy donors and enhancing cytotoxic responses to NKp30 crosslinking in NK cells from patients with NSCLC.ConclusionsCollectively, our work demonstrates superior activity of RLI compared with rhIL-15 in modulating and activating NK cells and provides additional evidences for a therapeutic strategy using RLI as antimetastatic molecule.

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Section: Discussionmentioning

confidence: 89%

IL-15 superagonist RLI has potent immunostimulatory properties on NK cells: implications for antimetastatic treatment

Desbois

Béal

Charrier

et al. 2020

J Immunother Cancer

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“…5 Systemic cellular inflammatory markers, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR) or lymphocyte/monocyte ratio (LMR), red cell distribution width (RDW), and prognostic nutritional index (PNI), may be potential prognostic factors for multiple solid tumors, including lung cancer, prostate cancer, gastric cancer, and metastatic melanoma. [6][7][8] However, the role of those peripheral blood inflammatory indicators in gliomas remains unclear and controversial. In a clinical study with 166 patients with GBM, both NLR and PLR are independent prognostic factors for OS, and a low NLR contributes to a better prognosis.…”

Section: Prognostic Role Of Inflammatory Markers In Gliomasmentioning

confidence: 99%

“…Numerous studies have indicated that systemic inflammatory responses can dramatically influence tumor growth, progression, and response to treatment . Systemic cellular inflammatory markers, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR) or lymphocyte/monocyte ratio (LMR), red cell distribution width (RDW), and prognostic nutritional index (PNI), may be potential prognostic factors for multiple solid tumors, including lung cancer, prostate cancer, gastric cancer, and metastatic melanoma . However, the role of those peripheral blood inflammatory indicators in gliomas remains unclear and controversial.…”

mentioning

confidence: 99%

Prognostic Significance of Preoperative Systemic Cellular Inflammatory Markers in Gliomas: A Systematic Review and Meta‐Analysis

Wang¹,

Kang

Lin

et al. 2019

Clinical Translational Sci

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Glioma is the most common malignant brain tumor and has high lethality. This tumor generated a robust inflammatory response that results in the deterioration of the disease. However, the prognostic role of systemic cellular inflammatory indicators in gliomas remains controversial. This meta‐analysis aimed to assess the prognostic significance of preoperative neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), red cell distribution width (RDW), and prognostic nutritional index (PNI) in patients with gliomas. Databases of PubMed, EMBASE, Web of Science, and The Cochrane Library were systematically searched for all studies published up to January 2019. Study screening and data extraction followed established Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. The Newcastle–Ottawa Scale was used to assess the quality of studies. Eighteen studies containing 3,261 patients were included. The analyses showed an increased NLR or RDW was found to be an independent predictor of worse survival in patients with gliomas (hazard ratio (HR): 1.38; 95% confidence interval (CI): 1.09–1.74; P = 0.008; and HR: 1.40; 95% CI: 1.13–1.74; P = 0.002, respectively). Furthermore, a higher PNI indicates a better overall survival (OS; HR: 0.57; 95% CI: 0.42–0.77; P = 0.0002). For the evaluation of PLR and LMR, none of these variables correlated with OS (P = 0.91 and P = 0.21, respectively). Our meta‐analysis indicates the NLR, RDW, and PNI rather than PLR and LMR are the independent index for predicting the OS of gliomas. Pre‐operative NLR, RDW, and PNI can help to evaluate disease progression, optimize treatment, and follow‐up in patients with gliomas.

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“…Certain rare mutations detected in the latter panel are absent in the Idylla EGFR test panel. However, the impact of this discrepancy on patient care is very low, as efficient and approved therapies are missing for those mutations [20,21]. Thus, these very rare mutations were not reported to be actionable for the different TKIs [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Targeted Assessment of the EGFR Status as Reflex Testing in Treatment-Naive Non-Squamous Cell Lung Carcinoma Patients: A Single Laboratory Experience (LPCE, Nice, France)

Lassalle

Hofman

Heeke

et al. 2020

Cancers

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Background: Assessment of actionable EGFR mutations is mandatory for treatment-naïve advanced or metastatic non-squamous lung carcinoma (NSLC), but the results need to be obtained in less than 10 working days. For rapid EGFR testing, an EGFR-specific polymerase chain reaction (PCR) assay is an alternative and simple approach compared to next generation sequencing (NGS). Here, we describe how a rapid EGFR-specific PCR assay can be implemented in a single laboratory center (LPCE, Nice, France) as reflex testing in treatment-naïve NSLC. Methods: A total of 901 biopsies from NSLC with more than 10% of tumor cells were prospectively and consecutively evaluated for EGFR mutation status between November 2017 and December 2019 using the Idylla system (Biocartis NV, Mechelen, Belgium). NGS was performed for nonsmokers with NSLC wild type for EGFR, ALK, ROS1, and BRAF and with less than 50% PD-L1 positive cells using the Hotspot panel (Thermo Fisher Scientific, Waltham, MA, USA). Results: Results were obtained from 889/901 (97%) biopsies with detection of EGFR mutations in 114/889 (13%) cases using the Idylla system. Among the 562 EGFR wild type tumors identified with Idylla, NGS detected one actionable and one nonactionable EGFR mutation. Conclusions: Rapid and targeted assessment of EGFR mutations in treatment-naïve NSLC can be implemented in routine clinical practice. However, it is mandatory to integrate this approach into a molecular algorithm that allows evaluation of potentially actionable genomic alterations other than EGFR mutations.

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Circulating innate immune markers and outcomes in treatment-naïve advanced non–small cell lung cancer patients

Cited by 35 publications

References 33 publications

IL-15 superagonist RLI has potent immunostimulatory properties on NK cells: implications for antimetastatic treatment

IL-15 superagonist RLI has potent immunostimulatory properties on NK cells: implications for antimetastatic treatment

Prognostic Significance of Preoperative Systemic Cellular Inflammatory Markers in Gliomas: A Systematic Review and Meta‐Analysis

Targeted Assessment of the EGFR Status as Reflex Testing in Treatment-Naive Non-Squamous Cell Lung Carcinoma Patients: A Single Laboratory Experience (LPCE, Nice, France)

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