Cited by 248Cytokine Signaling Pathways and InteractionsInflammatory Biomarkers in Disease PrognosisImmune cells in cancer

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Cytokine patterns in cancer patients: A review of the correlation between interleukin 6 and prognosis

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Lippitz, Bodo E., Harris, Robert A.·2016·OncoImmunology

DOI 10.1080/2162402x.2015.1093722PMC PMC4910721

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Abstract

OBJECTIVE: In tumor patients, IL-6 appears to be one component of a consistent cancer-associated cytokine network resulting in both a systemic immune stimulation and a microenvironment of cancer-induced immune suppression that ultimately protects the cancer cells. IL-6 has been associated with prognosis in cancer patients, but so far a systemical analysis has not been carried out. METHODS: The present meta-analysis studies the relation between IL-6 serum levels and the prognosis of cancer patients in the available clinical literature of 100 articles published between 1993 and 2013 comprising 11,583 patients. RESULTS: The IL-6 serum level was described as significantly correlating with survival in 82/101 series comprising 85.6% of patients (9917/11,583) with 23 different cancer types. A total of 64 studies dichotomized patient cohorts according to various cut-off IL-6 serum levels: in 59/64 of these series corresponding to 94.5% of the reported patients (7694/8142) significant correlations between IL-6 serum level and survival were seen. The median survival of cancer patients had been determined above various cut-off levels of serum IL-6 in 24 dichotomized studies (26 cohorts). There was a highly significant inverse correlation between median survival of the cohorts with IL-6 serum level above cut-off (1272 patients) and their corresponding IL-6 cut-off values (Spearman R -0,48 p= < 0.001) following a linear regression when both parameters were log-transformed (p < 0.001). A significant correlation between increasing serum IL-6 and tumor stage or metastases was described in 39/44 studies and 91% of published patients (4221/4636) where clinical parameters had been specified. CONCLUSIONS: Closely associated with the patient's clinical condition and independent of the cancer histology, the increased IL-6 serum level uniformly appears to correlate with survival as paraneoplastic condition in later cancer stages independent of the cancer type. Modifications of this paraneoplastic immune reaction may offer new therapeutic options in cancer.

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Figure 1. Median survival of 1272 cancer patients with IL-6 serum levels above various chosen cut-off values in 24 dichotomized studies (26 cohorts). Both x and y parameters have been have log-transformed in the graph. Sample size was used to weigh the studies. The median survival at chosen cut-off points was inversely correlated to the minimum IL-6 serum level at this cut-off, both when sample size was used to weigh the studies (p < 0.001) and also when the cohorts were not weighted (p < 0.005). Numbers indicate series as listed in Table 2.CC BY-NC · PubMed Central

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Authors: Lippitz, B. E., & Harris, R. A.
Affiliations: Karolinska University Hospital (SE)
Corresponding author: Lippitz, Bodo E.
ORCID: Lippitz, Bodo E.
Harris, Robert A.
Venue: OncoImmunology
Publisher: Informa UK Limited
Published: 2016-05-03
Volume: 5
Issue: 5
Pages: e1093722
ISSN: 2162-4011 (ISSN-L)
2162-402X
DOI: 10.1080/2162402x.2015.1093722
PMC: PMC4910721
OpenAlex: W2365037335
Cited by: 248
References: 165
Citations by year: 2026: 21 · 2025: 21 · 2024: 33 · 2023: 19 · 2022: 35 · 2021: 30 · 2020: 28 · 2019: 29 · 2018: 16 · 2017: 16
FWCI: 2.05
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/3.0/ (vor)
Locations: OncoImmunology (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: interleukin-6, serum IL-6, cancer prognosis, cancer survival, cytokine network, tumor microenvironment, immunosuppression, tumor stage, metastasis, cancer immunotherapy

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Cytokine patterns in cancer patients: A review of the correlation between interleukin 6 and prognosis

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