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. 2021 Jan-Dec:35:20587384211034089.
doi: 10.1177/20587384211034089.

Cytokines in various molecular subtypes of breast cancer

Alexsander Autenshlyus  1   2 , Kristina Davletova  1   2 , Nikolay Varaksin  3 , Igor Marinkin  1 , Vyacheslav Lyakhovich  2
Affiliations

Cytokines in various molecular subtypes of breast cancer

Alexsander Autenshlyus et al. Int J Immunopathol Pharmacol. 2021 Jan-Dec.

Abstract

Introduction: Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and functional characteristics of a tumor in terms of cytokine secretion remains unknown.

Methods: We studied spontaneous and mitogen-induced cytokine secretion by invasive breast carcinoma of no special type (IBC NST; cultured tumors and cultured peripheral blood cells), depending on a molecular tumor subtype (where "mitogens" means "polyclonal activators" (PA): phytohemagglutinin p, phytohemagglutinin M, concanavalin A, and Escherichia coli lipopolysaccharide). Enzyme-linked immunosorbent assays were used to determine concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 in culture supernatants of the tumors and peripheral blood cells.

Results: The luminal B HER2-positive molecular subtype of IBC NST was found to feature the highest spontaneous secretion of IL-6 and IL-8 and the highest mitogen-induced secretion of IL-6, IL-8, IL-1Ra, and TNF-α by tumors; the highest mitogen-induced secretion of IL-2, IL-6, IL-8, IL-1β, TNF-α, IFN-γ, and G-CSF by peripheral blood cells; and the highest cytokine-producing potential (the ratio of mitogen-induced to spontaneous secretion) of peripheral blood cells for the secretion of IL-6, IL-8, and IL-1Ra as compared to other molecular subtypes. The triple-negative subtype of IBC NST was characterized by the lowest cytokine-producing potential of tumors for the secretion of IL-6 and IL-8 as compared to other molecular subtypes as well as a lower "stimulation index of polyclonal activators" (calculated as (cytokine secretion after incubation with PA)/(spontaneous cytokine secretion)) for IL-18 secretion as compared to luminal subtypes. The XYZ correlated with a suppressive effect of PA on cytokine secretion by tumors of the triple-negative molecular subtype.

Conclusion: Therefore, our findings indicate that in IBC NST of luminal B HER2-positive and triple-negative molecular subtypes, the cytokine network has distinctive functional features.

Keywords: cytokines; invasive carcinoma of no special type; mitogens; molecular subtypes.

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Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
SIPA for cytokine secretion by cultured IBC NST tumors, depending on the molecular tumor subtype. Bars correspond to median ± interquartile range. ∗P = 2 × 10−2, ∗∗P = 1 × 10−2 as compared to the other molecular subtypes, #P = 1 × 10−2, ##P = 1 × 10−2 as compared to the luminal molecular subtypes. SIPA: stimulation index of polyclonal activators; IBC NST: invasive breast carcinoma of no special type.
Figure 2.
Figure 2.
SIPA for cytokine secretion by cultured peripheral blood cells, depending on the molecular tumor subtype of IBC NST. Bars correspond to median ± interquartile range. ∗P1–5 = 8 × 10−3, ∗∗P1–5 = 1 × 10−3, ∗∗∗P1–5 = 3 × 10−3, #P1–5 = 1 × 10−2, ##P1–5 = 1 × 10−2, ###P1–5 = 2 × 10−2 as compared to the other molecular subtypes. SIPA: stimulation index of polyclonal activators; IBC NST: invasive breast carcinoma of no special type.
Figure 3.
Figure 3.
Correlations between markers of molecular subtypes and the groups of cytokines secreted by a cultured tumor (A) or by cultured peripheral blood cells (B) from invasive breast carcinoma of no special type patients.
Figure 4.
Figure 4.
The cytokine network in luminal B HER2-positive (A) and triple-negative (B) molecular subtypes of breast cancer.
See this image and copyright information in PMC

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