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Metabolic Symbiosis and Immunomodulation: How Tumor Cell-Derived Lactate May
Disturb Innate and Adaptive Immune Responses
#MMPMID29629338
Morrot A
; da Fonseca LM
; Salustiano EJ
; Gentile LB
; Conde L
; Filardy AA
; Franklim TN
; da Costa KM
; Freire-de-Lima CG
; Freire-de-Lima L
Front Oncol
2018[]; 8
(?): 81
PMID29629338
show ga
The tumor microenvironment (TME) is composed by cellular and non-cellular
components. Examples include the following: (i) bone marrow-derived inflammatory
cells, (ii) fibroblasts, (iii) blood vessels, (iv) immune cells, and (v)
extracellular matrix components. In most cases, this combination of components
may result in an inhospitable environment, in which a significant retrenchment in
nutrients and oxygen considerably disturbs cell metabolism. Cancer cells are
characterized by an enhanced uptake and utilization of glucose, a phenomenon
described by Otto Warburg over 90?years ago. One of the main products of this
reprogrammed cell metabolism is lactate. "Lactagenic" or lactate-producing cancer
cells are characterized by their immunomodulatory properties, since lactate, the
end product of the aerobic glycolysis, besides acting as an inducer of cellular
signaling phenomena to influence cellular fate, might also play a role as an
immunosuppressive metabolite. Over the last 10?years, it has been well accepted
that in the TME, the lactate secreted by transformed cells is able to compromise
the function and/or assembly of an effective immune response against tumors.
Herein, we will discuss recent advances regarding the deleterious effect of high
concentrations of lactate on the tumor-infiltrating immune cells, which might
characterize an innovative way of understanding the tumor-immune privilege.
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