Blood Immune Cell Biomarkers in Lung Cancer Patients Undergoing Treatment with a Combination of Chemotherapy and Immune Checkpoint Blockade

Möller, Miriam; Turzer, Steffi; Ganchev, Georgi; Wienke, Andreas; Schütte, Wolfgang; Seliger, Barbara; Riemann, Dagmar

doi:10.3390/cancers14153690

Cited by 9 publications

(13 citation statements)

References 62 publications

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“…If the disease progressed early, before the expected time point 2, a sample of peripheral blood was collected when assessing the disease progression by CT. Complete blood counts, including absolute monocyte count (AMC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and platelet count, were recorded at the baseline (time point 1) and at the third cycle of combined therapy (time point 2) ( 19 ).…”

Section: Methodsmentioning

confidence: 99%

Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer

et al. 2023

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ObjectivesImmune-checkpoint inhibitors (ICIs) combined with chemotherapy are more widely used than monotherapy and have shown better survival in patients with advanced non-small cell lung cancer (NSCLC) without oncogenic driver alterations. The monocyte-to-lymphocyte ratio (MLR) might predict the treatment outcomes of ICI therapy in advanced NSCLC patients but has not yet been investigated. In addition, the cutoff of MLR is controversial. Therefore, the present study aimed to explore the associations between changes in MLR at the initial stage of treatment and clinical outcomes in stage IIIB-IV NSCLC patients receiving first-line PD-1 inhibitor combined with chemotherapy.MethodsThe present study included 139 stage IIIB-IV NSCLC patients treated with first-line PD-1 inhibitor combined with chemotherapy. The blood results were assessed 10 days before initiation of PD-1 inhibitor-based combination therapy (time point 1, baseline) and before the third cycle of combined therapy (time point 2). Compared to altered MLR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in baseline and in time point 2, patients were divided into decreased MLR/NLR/PLR and increased MLR/NLR/PLR groups. The objective response rate (ORR), progression-free survival (PFS), and the association with the changes in blood indicators were analyzed.ResultsA total of 48 patients were categorized in the decreased MLR group and 91 in the increased MLR group. Patients with decreased MLR had a significantly higher ORR in the univariate (P<0.001) and multivariate (P<0.001) Cox proportional hazards models. On the other hand, decreased MLR was significantly associated with prolonged PFS in the univariate (P=0.007) and multivariate (P=0.016) analyses. Next, 91 patients comprised the decreased NLR group and 48 as the increased NLR group. Patients with decreased NLR exhibited high ORR (P=0.001) and prolonged PFS in univariate analysis (P=0.033). Then, 64 patients comprised the decreased PLR group and 75 the increased PLR group. Decreased PLR was significantly associated with high ORR in univariate (P<0.001) and multivariate (P=0.017) analyses. The subgroup analyses showed that decreased MLR was significantly associated with satisfactory outcomes in patients with all PD-L1 expressions.ConclusionDecreased MLR was associated with high ORR and long PFS and might have a potential predictive value in patients with stage IIIB-IV NSCLC treated with first-line PD-1 inhibitor combined with chemotherapy. In addition, changes in MLR might have predictive value in all PD-L1-expressing populations. Decreased NLR and PLR also showed improved survival, suggesting that changes in NLR and PLR may be complementary to predicting prognosis.

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Section: Methodsmentioning

confidence: 99%

Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer

et al. 2023

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“…All patients gave written informed consent for the study's proposal and procedures. In a former study, 90 patients with histologically confirmed unresectable locally advanced or metastatic lung cancer, prior to PD-1 or PD-L1 blockade treatment in combination with chemotherapy, were prospectively enrolled from June 2019 to June 2021 (Table 1 in [11]). In total, 12 of the 36 patients surviving ≥ 12 months consented to a third blood draw and were included in the current pilot study.…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples, antibody staining, and flow cytometry. Blood samples of a former study [11] were collected before the initiation of immune/chemotherapy (time point 0, baseline) and prior to the third therapy cycle (t 1 ). For the current pilot study, 12 patients with an OS of at least 12 months consented to a third blood draw (t 2 ).…”

Section: Methodsmentioning

confidence: 99%

“…Blood-based cellular immune biomarkers have shown great promise in predicting responses to ICI therapies due to easy specimen accessibility, the opportunity for serial monitoring, quantitative measurement, and the availability of unique analytic high-throughput (single cell) platforms [10]. In a recent study [11], we found that NSCLC patients with a baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 6.1, ≥ 22% HLA-DR low monocytes, a frequency of slan+ non-classical monocytes < 0.25% of leukocytes, and/or amounts of dendritic cells (DC) ≤ 0.14% of leukocytes showed poor progression-free survival (PFS). In this study, the four blood cell biomarkers were monitored in patients with advanced NSCLC surviving at least 12 months of a combined ICI/chemotherapy to investigate whether these markers are useful to predict the treatment outcomes of patients.…”

Section: Introductionmentioning

confidence: 99%

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Blood Immune Cells as Biomarkers in Long-Term Surviving Patients with Advanced Non-Small-Cell Lung Cancer Undergoing a Combined Immune/Chemotherapy

Möller,

Schütte,

Turzer

et al. 2023

Cancers

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An important challenge remains in identifying the baseline characteristics of cancer patients who will mostly benefit from immune checkpoint inhibitor (ICI) therapies. Furthermore, biomarkers could help in the choice of an optimal therapy duration after a primary therapy response. In this pilot study, the time courses of four different immune cell parameters were followed in 12 patients with advanced non-small-cell lung cancer (NSCLC) undergoing ICI therapy combined with chemotherapy and surviving at least 12 months. Blood was collected at the time point of the first and third antibody administration, as well as after 12 months of patients’ survival. Using multi-color flow cytometry, two suppressive markers (neutrophil/lymphocyte ratio (NLR) and the frequency of circulating HLA-DRlow monocytes), as well as two markers of an ongoing immune response (6-Sulfo LacNAc (slan)+ non-classical monocytes and dendritic cell (DC) subtypes), were determined. In most of those who survived > 12 months, a low NLR and a low number of HLA-DRlow monocytes combined with clearly detectable numbers of slan+ non-classical monocytes and of DC subtypes were seen. Two of the patients had an increase in the suppressive markers paired with a decrease in slan+ non-classical monocytes and in DC subtypes, which, in at least one patient, was the correlate of an ongoing clinical progression. Our results implicate that the NLR, specific subtypes of monocytes, and the number of blood DCs might be useful predictive biomarkers for cancer patients during long-term treatment with ICI/chemotherapy.

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“…Apart from reporting NLR and PLR, other blood cell counts included derived neutrophil-lymphocyte ratio (dNLR), absolute lymphocyte count (ALC), absolute neutrophil count (ANC), absolute platelet count (APC), absolute eosinophil count (AEC), and leukocyte count and its differentials. Receiver operating characteristic (ROC) curves were used in nine studies (25,33,36,(38)(39)(40)(41)(42)(43) to determine the optimal cutoff value for NLR and PLR.…”

Section: Research Characteristicsmentioning

confidence: 99%

Neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as potential predictive markers of treatment response in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Rugambwa,

Abdihamid,

Zhang

et al. 2023

Front. Oncol.

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BackgroundThe role of platelet–lymphocyte ratio (PLR) and neutrophil–lymphocyte ratio (NLR) as independent prognostic markers in different tumors is well established. However, there is a limited review of the potential of NLR and PLR as predictors of treatment outcomes from immune checkpoint inhibitors (ICIs).ObjectiveTo establish a correlation between NLR and PLR and the potential of clinical benefit from ICIs.MethodsThe literature search was performed for studies that reported the association between NLR, PLR, and treatment outcomes among cancer patients treated with ICIs. The outcomes of interest were objective response rate (ORR), disease control rate (DCR), and progressive disease (PD). ORR was the summation of patients who achieved complete response and partial response. DCR included patients who achieved stable disease. PD was the proportion of patients who progressed, relapsed, or discontinued the treatment. Statistical analysis was performed using the STATA 12.0 package. Heterogeneity was determined by the I2 value. Quality assessment was performed using the Newcastle–Ottawa Scale. Egger’s test was used to establish publication bias and sensitivity analysis.ResultsA total of 40 papers that met the inclusion criteria were included in the systematic review. However, only 17 studies were used in the meta-analysis to determine the correlation between NLR, PLR, and treatment response. We found that treatment with ICIs and monitoring of outcomes and adverse events using PLR and NLR parameters have been studied in different tumors. Our analysis showed that low NLR correlated with higher ORR (OR = 0.62 (95% CI 0.47–0.81, p = 0.001) and higher DCR (OR = 0.23, 95% CI 0.14–0.36, p < 0.001). Higher NLR predicted a higher probability of PD (OR = 3.12, 95% CI 1.44, 6.77, p = 0.004). Similarly, low PLR correlated with higher ORR (OR = 0.69, 95% CI 0.5, 0.95, p = 0.025). Generally, patients with low NLR and PLR were more likely to achieve clinical benefit and better response (p-value < 0.001). Meanwhile, patients with high ratios were more likely to progress (p-value < 0.005), although there was significant heterogeneity among studies. There was no significant publication bias observed.ConclusionThe study showed that high NLR and PLR either at baseline or during treatment is associated with poorer treatment outcome. Therefore, these ratios can be utilized in clinical practice with other markers to determine treatment efficacy from immunotherapy.

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Blood Immune Cell Biomarkers in Lung Cancer Patients Undergoing Treatment with a Combination of Chemotherapy and Immune Checkpoint Blockade

Cited by 9 publications

References 62 publications

Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer

Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer

Blood Immune Cells as Biomarkers in Long-Term Surviving Patients with Advanced Non-Small-Cell Lung Cancer Undergoing a Combined Immune/Chemotherapy

Neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as potential predictive markers of treatment response in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

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