Prognostic Value of Baseline Neutrophil-to-Lymphocyte Ratio in Outcome of Immune Checkpoint Inhibitors

Xie, Xianhe; Liu, Junjin; Huang, Yang; Chen, Huijuan; Zhou, Sijing; Lin, Heng; Liao, Ziyuan; Ding, Ying; Ling, Liting; Wang, Xuewen

doi:10.1080/07357907.2019.1639057

Cited by 37 publications

(32 citation statements)

References 39 publications

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“…This hypothesis has been proved by a meta-analysis performed by Cao et al, which showed that higher baseline NLR was associated with poor progression free survival (PFS) [10 studies: hazard ratios (HR) = 1.44; 95% confidence interval (CI) = 1.18 – 1.77; P < .05] and OS (8 studies: HR = 1.75; 95% CI: 1.33 – 2.30; P < .05) in patients with NSCLC after nivolumab treatment. [ 13 ] The similar conclusion was also verified in NSCLC stratification of meta-analysis studies focusing on all cancer types (Tan et al [ 14 ] : 4 articles; Sacdalan et al [ 15 ] : 3 articles; Xie et al [ 16 ] : 6 articles). However, the literature size in these meta-analyses seemed to be small and abundant negative associations of NLR with OS or PFS were observed in the recent studies [ 17 – 20 ] published in 2019 which were not included previously.…”

Section: Introductionsupporting

confidence: 56%

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The prediction potential of neutrophil-to-lymphocyte ratio for the therapeutic outcomes of programmed death receptor-1/programmed death ligand 1 inhibitors in non-small cell lung cancer patients

Huang

Shen

2020

Medicine

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Background: Programmed death receptor-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have been demonstrated to improve the prognosis of patients with advanced non-small cell lung cancer (NSCLC) compared with chemotherapy. However, there were still some non-responders. Thus, how to effectively screen the responder may be an important issue. Recent studies revealed the immune-related indicator, neutrophil-lymphocyte ratio (NLR), may predict the therapeutic effects of anti-PD1/PD-L1 antibodies; however, the results were controversial. This study was to re-evaluate the prognostic potential of NLR for NSCLC patients receiving PD1/PD-L1 inhibitors by performing a meta-analysis. Methods: Eligible studies were identified by searching online databases of PubMed, EMBASE and Cochrane Library. The predictive values of NLR for overall survival, (OS), progression free survival (PFS) and overall response rate (ORR) were estimated by hazard ratio (HR) with 95% confidence interval (CI). Results: Twenty-four studies involving 2196 patients were included. The pooled analysis demonstrated that elevated NLR before PD-1/PD-L1 inhibitor treatment was a predictor of poor OS (HR = 2.17; 95% CI: 1.64 – 2.87, P < .001), PFS (HR = 1.54; 95% CI: 1.34 – 1.78, P < .001) and low ORR (HR = 0.64; 95% CI: 0.44 – 0.95, P = .027) in NSCLC patients. Subgroup analysis revealed the predictive ability of NLR for OS and PFS was not changed by ethnicity, sample size, cut-off, HR source, study design or inhibitor type (except the combined anti-PD-L1 group); while its association with ORR was only significant when the cut-off value was less than 5 and the studies were prospectively designed. Conclusion: Our findings suggest patients with lower NLR may benefit from the use of PD-1/PD-L1 inhibitors to prolong their survival period.

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Section: Introductionsupporting

confidence: 56%

“…Although there were meta-analyses to investigate the prognostic value of NLR for anti-PD-1/PD-L1 treatment in NSCLC patients, [ 13 – 16 ] their sample size was relatively small (≤ 10). In the present study, a total of 24 publications involving 2196 patients were included to perform an updated meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

The prediction potential of neutrophil-to-lymphocyte ratio for the therapeutic outcomes of programmed death receptor-1/programmed death ligand 1 inhibitors in non-small cell lung cancer patients

Huang

Shen

2020

Medicine

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“…TAN have been described to enhance tumor angiogenesis and promote metastasis [60]. High neutrophil to lymphocyte ratio (≥4) at the baseline is considered as a powerful prognostic factor associated with reduced PFS and OS in melanoma patients treated with immune checkpoint inhibitors [61,62].…”

Section: Neutrophilsmentioning

confidence: 99%

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Petrova

Arkhypov

Weber

et al. 2020

IJMS

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Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms, including negative immune checkpoint molecules. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.

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“…The neutrophil-to-lymphocyte ratio (NLR) is related to systemic inflammation, as an elevated number of neutrophils was reported in the peripheral blood of cancer patients [ 100 , 101 ]. High pre-treatment NLRs were related to worse OS for melanoma patients treated with ipilimumab (NLR > 3–5), nivolumab (NLR > 2–5), and the combination of nivolumab and ipilimumab (NLR > 4.7) [ 102 , 103 , 104 , 105 , 106 , 107 ]. Moreover, an increase of NLR over 30% during two cycles of anti-PD-1 treatment was related to lower OS in melanoma patients (47 vs. 13.5 months, p < 0.001) [ 108 ].…”

Section: Predictive Biomarkers Related To the Host Immune Systemmentioning

confidence: 99%

The Tumor and Host Immune Signature, and the Gut Microbiota as Predictive Biomarkers for Immune Checkpoint Inhibitor Response in Melanoma Patients

Tomela

Pietrzak

Schmidt

et al. 2020

Life

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There are various melanoma treatment strategies that are based on immunological responses, among which immune checkpoint inhibitors (ICI) are relatively novel form. Nowadays, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies represent a standard treatment for metastatic melanoma. Although there are remarkable curative effects in responders to ICI therapy, up to 70% of melanoma patients show resistance to this treatment. This low response rate is caused by innate as well as acquired resistance, and some aspects of treatment resistance are still unknown. Growing evidence shows that gut microbiota and bacterial metabolites, such as short-chain fatty acids (SCFAs), affect the efficacy of immunotherapy. Various bacterial species have been indicated as potential biomarkers of anti-PD-1 or anti-CTLA-4 therapy efficacy in melanoma, next to biomarkers related to molecular and genetic tumor characteristics or the host immunological response, which are detected in patients’ blood. Here, we review the current status of biomarkers of response to ICI melanoma therapies, their pre-treatment predictive values, and their utility as on-treatment monitoring tools in order to select a relevant personalized therapy on the basis of probability of the best clinical outcome.

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Prognostic Value of Baseline Neutrophil-to-Lymphocyte Ratio in Outcome of Immune Checkpoint Inhibitors

Cited by 37 publications

References 39 publications

The prediction potential of neutrophil-to-lymphocyte ratio for the therapeutic outcomes of programmed death receptor-1/programmed death ligand 1 inhibitors in non-small cell lung cancer patients

The prediction potential of neutrophil-to-lymphocyte ratio for the therapeutic outcomes of programmed death receptor-1/programmed death ligand 1 inhibitors in non-small cell lung cancer patients

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

The Tumor and Host Immune Signature, and the Gut Microbiota as Predictive Biomarkers for Immune Checkpoint Inhibitor Response in Melanoma Patients

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