Is the Neutrophil-to-Lymphocyte Ratio a Useful Prognostic Indicator in Melanoma Patients?

Cohen, Joshua T.; Vezeridis, Michael P.

doi:10.2217/mmt-2020-0006

Cited by 30 publications

(28 citation statements)

References 74 publications

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“…Parameters such as NLR, PLR, LMR and SII are markers associated with the inflammatory process, and inflammation plays a key role in the pathophysiology of many diseases, including cancer 21 . Patients with advanced cancer usually show changes in peripheral blood cell composition that are suggestive of an expansion in the myeloid component (neutrophils, platelets, and monocytes) and a reduction in the lymphoid compartment 22 . These changes in peripheral blood reflect the situation in the tumour environment.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of blood cell count-derived ratios in BRAF-mutated metastatic melanoma

et al. 2022

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Background. The treatment and prognosis of metastatic melanoma have changed during the last decade to include immunotherapy or targeted therapy as standard therapeutic options for BRAF-mutated melanoma. However, predictive and/or prognostic markers are lacking, especially in clinical situations where several options are available. The aim of this study was to determine the association of pre-therapeutic blood cell count-derived ratios (BCDR) with survival in patients with BRAF-mutated metastatic melanoma. Methods. We evaluated the prognostic role of BCDR in therapy-naïve patients with BRAF-mutated metastatic melanoma treated with immune checkpoint inhibitors or targeted therapy. The impact of BCDR on survival was analysed using univariate and multivariate Cox proportional hazard models. Results. We enrolled 46 patients treated with BRAF inhibitors and 20 patients who received anti-PD-1 checkpoint inhibitors. The median progression-free survival (PFS) and overall survival (OS) were 8.3 and 18.2 months, respectively, with no statistical difference between groups. The objective response rate was 39% (30% in the anti-PD-1 and 44% in the targeted therapy groups). Baseline BCDR values were associated with improved PFS and OS in the immunotherapy group. Only the platelet-to-lymphocyte ratio (PLR) was associated with OS and PFS in the targeted therapy group. Independent prognostic indicators for PFS were lactate dehydrogenase, PLR and the lymphocyte-to-monocyte ratio (LMR) and those for OS were LMR, toxicity and the number of initial metastases. Conclusion. BCDR had a substantial prognostic value in patients with BRAF-mutated metastatic melanoma treated with immune checkpoint inhibitors. However, a prognostic role for BCDR seemed less apparent in patients treated with targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of blood cell count-derived ratios in BRAF-mutated metastatic melanoma

et al. 2022

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“…While regulatory T cells play pro-tumorigenic roles; CD8 + T cells, CD4 + T cells, γδ T cells, and NK cells have been shown to act against the transformed cells, [ 38 , 43 , 46 , 47 , 58 , 64 , 73 , 118 ]. Conversely neutrophils and myeloid-derived suppressor cells have been associated with poor prognosis and are largely pro-tumorigenic [ 22 , 28 , 69 , 126 , 129 , 145 , 155 ]. Our data shows that sensory overactivation induce an increase in the number of tumor-infiltrating anti-cancer lymphocytes (CD8 + T cells, CD4 + T cells, γδ T cells, and NK cells), while we did not detect changes in the number of tumor-infiltrating regulatory T cells.…”

Section: Discussionmentioning

confidence: 99%

Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression

Costa

Silva

Prazeres

et al. 2021

acta neuropathol commun

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Sensory neurons have recently emerged as components of the tumor microenvironment. Nevertheless, whether sensory neuronal activity is important for tumor progression remains unknown. Here we used Designer Receptors Exclusively Activated by a Designer Drug (DREADD) technology to inhibit or activate sensory neurons’ firing within the melanoma tumor. Melanoma growth and angiogenesis were accelerated following inhibition of sensory neurons’ activity and were reduced following overstimulation of these neurons. Sensory neuron-specific overactivation also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of melanoma biopsies revealed that increased expression of sensory neurons-related genes within melanoma was associated with improved survival. These findings suggest that sensory innervations regulate melanoma progression, indicating that manipulation of sensory neurons’ activity may provide a valuable tool to improve melanoma patients’ outcomes.

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“…Further, elevated NLR is associated with low rates of response to ICI across multiple solid cancers including non-small cell lung cancer (NSCLC) [ 80 ], breast cancer [ 81 ], metastatic melanoma [ 82 ], prostate cancer [ 83 ], CRC [ 84 ], PDAC [ 85 ], renal cell carcinoma (RCC) [ 86 ], HCC [ 87 ], cholangiocarcinoma [ 88 ], ovarian cancer [ 89 ], and sarcoma [ 90 ]. Neutrophilia with an NLR ≥4 correlates with inferior disease-free survival (DFS) and OS in patients with mesothelioma, PDAC, RCC, and CRC as well as cancer-associated thrombosis [ 91 – 93 ].…”

Section: Prognostic Value Of Neutrophil-to-lymphocyte Ratio and Circu...mentioning

confidence: 99%

Neutrophils and polymorphonuclear myeloid-derived suppressor cells: an emerging battleground in cancer therapy

et al. 2022

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Neutrophils are central mediators of innate and adaptive immunity and first responders to tissue damage. Although vital to our health, their activation, function, and resolution are critical to preventing chronic inflammation that may contribute to carcinogenesis. Cancers are associated with the expansion of the neutrophil compartment with an escalation in the number of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in the peripheral circulation and tumor microenvironment. Although phenotypically similar to classically activated neutrophils, PMN-MDSC is pathologically activated and immunosuppressive in nature. They dynamically interact with other cell populations and tissue components and convey resistance to anticancer therapies while accelerating disease progression and metastatic spread. Cancer-associated neutrophilia and tumor infiltration of neutrophils are significant markers of poor outcomes in many cancers. Recently, there has been significant progress in the identification of molecular markers of PMN-MDSC providing insights into the central role of PMN-MDSC in the local tumor microenvironment as well as the systemic immune response in cancer. Further advances in sequencing and proteomics techniques will improve our understanding of their diverse functionalities and the complex molecular mechanisms at play. Targeting PMN-MDSC is currently one of the major focus areas in cancer research and several signaling pathways representing possible treatment targets have been identified. Positive results from preclinical studies clearly justify the current investigation in drug development and thus novel therapeutic strategies are being evaluated in clinical trials. In this review, we discuss the involvement of PMN-MDSC in cancer initiation and progression and their potential as therapeutic targets and clinical biomarkers in different cancers.

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Is the Neutrophil-to-Lymphocyte Ratio a Useful Prognostic Indicator in Melanoma Patients?

Cited by 30 publications

References 74 publications

Prognostic value of blood cell count-derived ratios in BRAF-mutated metastatic melanoma

Prognostic value of blood cell count-derived ratios in BRAF-mutated metastatic melanoma

Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression

Neutrophils and polymorphonuclear myeloid-derived suppressor cells: an emerging battleground in cancer therapy

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