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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      The prognostic value of systemic and local inflammation in patients with laryngeal squamous cell carcinoma

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          Abstract

          Background

          Cancer-related systemic inflammation has been demonstrated to be associated with poor outcome in multiple types of cancers. Meanwhile, the local inflammation, which is characterized by dense intratumoral immune infiltrate, is a favorable predictor of survival outcome.

          Purpose

          To evaluate the role of systemic and local inflammation in predicting outcome in patients with laryngeal squamous cell carcinoma.

          Patients and methods

          In this retrospective study, 120 patients who had undergone postoperative radiotherapy were enrolled. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as calculated from pretreatment whole blood counts, were used to indicate systemic inflammation. The optimal cutoff values of NLR and PLR were determined using receiver operating characteristic curve analysis. Tumor infiltrating lymphocytes (TILs) density, as assessed by pathologist review of hematoxylin and eosin-stained slides, was used to represent local inflammation. Overall survival (OS) and recurrence-free survival (RFS) were assessed using the Kaplan–Meier method and multivariate Cox regression analysis.

          Results

          The best cutoff was 2.79 for NLR and 112 for PLR. Kaplan–Meier analysis revealed that high NLR, high PLR, and low TILs density were significantly correlated with inferior OS and RFS, respectively (all P<0.05). The Cox proportional multivariate hazard model showed that a high pretreatment PLR and a low TILs density were both independently correlated with poor OS and RFS, respectively (all P<0.05).

          Conclusion

          Markers of systemic and local inflammation, especially PLR and TILs density, are reliable prognostic factors in patients with laryngeal squamous cell carcinoma.

          Most cited references27

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          The platelet contribution to cancer progression.

          N M Bambace, C. Holmes (2011)
          Traditionally viewed as major cellular components in hemostasis and thrombosis, the contribution of platelets to the progression of cancer is an emerging area of research interest. Complex interactions between tumor cells and circulating platelets play an important role in cancer growth and dissemination, and a growing body of evidence supports a role for physiologic platelet receptors and platelet agonists in cancer metastases and angiogenesis. Platelets provide a procoagulant surface facilitating amplification of cancer-related coagulation, and can be recruited to shroud tumor cells, thereby shielding them from immune responses, and facilitate cancer growth and dissemination. Experimental blockade of key platelet receptors, such as GP1b/IX/V, GPIIbIIIa and GPVI, has been shown to attenuate metastases. Platelets are also recognized as dynamic reservoirs of proangiogenic and anti-angiogenic proteins that can be manipulated pharmacologically. A bidirectional relationship between platelets and tumors is also seen, with evidence of 'tumor conditioning' of platelets. The platelet as a reporter of malignancy and a targeted delivery system for anticancer therapy has also been proposed. The development of platelet inhibitors that influence malignancy progression and clinical testing of currently available antiplatelet drugs represents a promising area of targeted cancer therapy. © 2011 International Society on Thrombosis and Haemostasis.
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            Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma.

            Nghia Nguyen-Huu, Emily L Bellile, Daffyd Thomas … (2016)
            Because immune responses within the tumor microenvironment are important predictors of tumor biology, correlations of types of tumor infiltrating lymphocytes (TILs) with clinical outcomes were determined in 278 patients with head and neck squamous cell carcinoma (HNSCC).
            Article 0 comments Cited 156 times – based on 0 reviews     Review now
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              Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer

              Nathan West, Katy Milne, Pauline T Truong … (2011)
              Introduction Infiltration of breast tumors by tumor-infiltrating lymphocytes (TIL) has been associated with sensitivity to anthracycline-based chemotherapy. However, it is unclear whether this is true within the estrogen receptor-alpha (ER)-negative subset of breast tumors that frequently manifest high TIL levels. Methods The association of TIL with short-term and long-term clinical response to anthracycline-based therapy was assessed in two independent ER-negative breast cancer cohorts in which patients were categorized as TIL-high or TIL-low. We defined an eight-gene lymphocyte mRNA expression signature (including CD19, CD3D, CD48, GZMB, LCK, MS4A1, PRF1, and SELL) and used unsupervised hierarchical clustering to examine the association between TIL and short-term response to neoadjuvant chemotherapy in a previously published cohort of ER-negative tumors (n = 113). We also examined the association between TIL and long-term chemotherapeutic efficacy in a second cohort of ER-negative tumors (n = 255) with longer than 6 years of median follow-up by using tissue microarrays and immunohistochemistry (IHC) for detection of CD3, CD8, CD4, CD20, and TIA-1. Results In patients with ER-negative tumors treated with neoadjuvant anthracycline-based chemotherapy, pathologic complete responses (pCRs) were achieved by 23 (74%) of 31 TIL-high patients and 25 (31%) of 80 TIL-low patients (odds ratio (OR), 6.33; 95% confidence interval (CI), 2.49 to 16.08; P < 0.0001). Multivariate logistic regression with standard clinicopathologic features demonstrated that only tumor size (P = 0.037) and TIL status (P = 0.001) were independent predictors of anthracycline response. In the second cohort, adjuvant anthracycline-based therapy was associated with increased disease-free survival (DFS) only in patients with high levels of intraepithelial CD3+ TIL (P = 0.0023). In contrast, outcomes after CMF treatment (cyclophosphamide, methotrexate, and fluorouracil) showed no association with CD3 status. In both cohorts, cytotoxic T-cells were the primary TIL subtype associated with anthracycline sensitivity. Finally, TIL significantly predicted anthracycline sensitivity for both the Her2-positive and triple-negative tumor phenotypes. Conclusions ER-negative breast cancers with high levels of TIL have heightened sensitivity to anthracycline-based chemotherapy, as assessed by the immediate response to neoadjuvant therapy and long-term outcome following adjuvant therapy. Investigations of TIL-based predictive tests to identify patients likely to benefit from anthracycline-based treatments are warranted.
              Article 0 comments Cited 134 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): OncoTargets and Therapy
                Title: OncoTargets and therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1178-6930
                Publication date Collection: 2016
                Publication date (Electronic): 21 November 2016
                Volume: 9
                Pages: 7177-7185
                Affiliations
                [1 ]Department of Radiation Oncology, Eye, Ear, Nose, and Throat Hospital, Fudan University
                [2 ]Department of Pathology, Shanghai Medical School, Fudan University
                [3 ]Department of Pathology, Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, People’s Republic of China
                Author notes
                Correspondence: Shengzi Wang, Department of Radiation Oncology, Eye, Ear, Nose, and Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, People’s Republic of China, Tel +86 189 1776 1761, Email shengziwang@ 123456fudan.edu.cn
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: ott-9-7177
                DOI: 10.2147/OTT.S113307
                PMC ID: 5123657
                PubMed ID: 27920556
                SO-VID: 0603aa60-e283-407d-8424-72bd5905dada
                Copyright © © 2016 Wang et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: laryngeal squamous cell carcinoma,systemic inflammation,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,tumor infiltrating lymphocytes
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: laryngeal squamous cell carcinoma, systemic inflammation, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, tumor infiltrating lymphocytes

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