The neutrophil-to-lymphocyte ratio: a narrative review

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Abstract

Cellular-mediated inflammatory response, lymphocytes, neutrophils, and monocytes are increasingly being recognised as having an important role in tumorigenesis and carcinogenesis. In this context, studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) can be used as an independent prognostic factor in a variety of cancers. Particularly in breast cancer, several studies have shown that a high NLR is associated with shorter survival. Because the NLR can be easily determined from the full blood count, it could potentially provide a simple and inexpensive test cancer prognosis. This review addresses the possibilities and limitations of using the NLR as a clinical tool for risk stratification helpful for individual treatment of breast cancer patients. The potential underlying phenomena and some perspectives are discussed.

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Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer.

Carsten Denkert, Sibylle Loibl, Aurelia Noske … (2010)

PURPOSE Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. METHODS We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell-related markers CD3D and CXCL9 with pCR. CONCLUSION The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy.

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Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

Jadwiga Jablonska, Sara Leschner, Kathrin Westphal … (2010)

Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.

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The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients

S Krenn-Pilko, U Langsenlehner, E-M Thurner … (2014)

Background: The elevation of the platelet-to-lymphocyte ratio (PLR), an easily applicable blood test based on platelet and lymphocyte counts has been associated with poor prognosis in patients with different types of cancer. The present study was aimed to investigate the prognostic significance of the preoperative PLR in a large cohort of breast cancer patients. Methods: Data from 793 consecutive non-metastatic breast cancer patients, treated between 1999 and 2004, were evaluated retrospectively. The optimal cutoff values for the PLR were calculated using receiver operating curve analysis. Cancer-specific survival (CSS), overall survival (OS) as well as distant metastasis-free survival (DMFS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of PLR, multivariable Cox regression models were applied for all three different end points. Results: Univariable analysis revealed a significant association between the elevated preoperative PLR and CSS (hazard ratio (HR): 2.75, 95% confidence interval (CI): 1.57–4.83, P<0.001) that remained statistically significant in multivariable analysis (HR: 2.03, 95% CI: 1.03–4.02, P=0.042). An increased PLR was also significantly associated with decreased OS in univariable (HR: 2.45, 95% CI: 1.43–4.20, P=0.001) and in multivariable analysis (HR: 1.92, 95% CI: 1.01–3.67, P=0.047). Furthermore, univariable analysis showed a significant impact of increased PLR on DMFS (HR: 2.02, 95% CI: 1.18–3.44, P=0.010). Subgroup analysis revealed significant associations of the elevated PLR on the primary end point CSS for all breast cancer subtypes. This association retained its significance in multivariable analysis in patients with luminal B tumours (HR: 2.538, 95% CI: 1.043–6.177, P=0.040). Conclusions: In this study, we identified the preoperative PLR as an independent prognostic marker for survival in breast cancer patients. Independent validation of our findings is needed.

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Journal ID (nlm-ta): Ecancermedicalscience

Journal ID (iso-abbrev): Ecancermedicalscience

Journal ID (publisher-id): ecancermedicalscience

Title: ecancermedicalscience

Publisher: Cancer Intelligence

ISSN (Electronic): 1754-6605

Publication date Collection: 2016

Publication date (Electronic): 12 December 2016

Volume: 10

Electronic Location Identifier: 702

Affiliations

[1 ]Mastology Program, Federal University of Uberlandia (UFU), Avenida Engenheiro Diniz 1178, Reitoria 3º Andar Uberlândia, Minas Gerais, Brazil

[2 ]Department of Medical Oncology, AC Camargo Cancer Center, R Professor Antônio Prudente, 211, Liberdade, São Paulo 01509, Brazil

[3 ]Laboratory of Biochemistry of Protein Chemistry (Proteomics Research), University of Brasilia (UnB), Campus Universitário Darcy Ribeiro S/N (Asa Norte) 70910-900, Brazil

[4 ]Mastology Program, Federal University of Goias (UFG), Rodovia Goiania Nerópolis Km 12, Prédio da Reitoria, 74001-970, Goiania/GO, Brazil

[5 ]Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA

[6 ]Department of Anesthesiology and Perioperative Medicine, Universitair Ziekenhuis Brussel, laarbeeklaan 101, 1090 Brussels, Belgium

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Correspondence to: Patrice Forget. forgetpatrice@ 123456yahoo.fr

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Publisher ID: can-10-702

DOI: 10.3332/ecancer.2016.702

PMC ID: 5221645

PubMed ID: 28105073

SO-VID: 6dbd5a43-6d34-409d-a5a8-781ead7b0873

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The neutrophil-to-lymphocyte ratio: a narrative review

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Most cited references 26

Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer.

Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients

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