Chronic alcohol consumption enhances myeloid-derived suppressor cells in B16BL6 melanoma-bearing mice

Abstract

We previously found that chronic alcohol consumption decreases the survival of mice bearing subcutaneous B16BL6 melanoma. The underlying mechanism is still not completely understood. Antitumor T cell immune responses are important to inhibiting tumor progression and extending survival. Therefore, we examined the effects of chronic alcohol consumption on the functionality and regulation of these cells in C57BL/6 mice that chronically consumed 20% (w/v) alcohol and subsequently were inoculated subcutaneously with B16BL6 melanoma cells. Chronic alcohol consumption inhibited melanoma-induced memory T cell expansion and accelerated the decay of interferon (IFN)-γ producing T cells in the tumor-bearing mice. Foxp3 + CD4 + CD25 + regulatory T cells were not affected; however, the percentage of myeloid-derived suppressor cells (MDSC) was significantly increased in the peripheral blood and spleen. T cell proliferation as determined by carboxyfluorescein succinimidyl ester labeling experiments in vitro was inhibited by alcohol consumption relative to control water-drinking melanoma-bearing mice. Collectively, these data show that chronic alcohol consumption inhibits proliferation of memory T cells, accelerates the decay of IFN-γ producing CD8 + T cells, and increases MDSC, all of which could be associated with melanoma progression and reduced survival.

Chronic alcohol consumption inhibits melanoma growth but decreases the survival of mice immunized with tumor cell lysate and boosted with α-galactosylceramide

“…The present study further supports the concept that chronic alcohol consumption accelerates the dysfunction of the immune system in the melanoma-bearing mice such as skewing iNKT cell cytokine profile from Th1-dominant to Th2 dominant as we reported in the present study, and inhibiting tumor-specific CD8 + T cell expansion and accelerating the decay of IFN-γ-producing CD8 + T cells as previously reported [26]. Although we found that alcohol consumption inhibits tumor growth and that immunization with a melanoma lysate further inhibits the growth of tumor in alcohol-consuming mice (Fig.…”

“…Immunization could further accelerate and amplify this process. Additional evidence supporting this is our previous finding that alcohol consumption accelerates the dysfunction of CD8 + T cells within two weeks after melanoma inoculation [26]. These functional changes in the immune system are reflected in the lack of a survival benefit in the melanoma-bearing mice.…”

“…The percentage of IFN-γ-producing T cells in the alcohol-consuming mice continues to be elevated up to 11 days after s.c. melanoma inoculation as compared to water-drinking mice [26]. It is well-known that the immune system plays an important role in the control of tumor growth.…”

“…A large body of data indicates that chronic alcohol consumption in humans and mice activates the immune system, which is reflected in the activation of CD8 + T cells, dendritic cells (DC), and NKT cells, and increased production of pro-inflammatory cytokines such as IFN-γ and TNF-α [21-25]. We found that chronic alcohol consumption along with advancing growth of s.c. melanoma leads to inhibition in the expansion of memory and melanoma-specific CD8 + T cells, acceleration in the decay of Th1 cytokine producing CD8 + T cells [26], and compromised circulation of mature B cells [27]. Chronic alcohol consumption also increases invariant NKT (iNKT) cells and especially IFN-γ-producing iNKT cells [28] [29].…”

Alcohol Consumption and Antitumor Immunity: Dynamic Changes from Activation to Accelerated Deterioration of the Immune System

“…These enzymes metabolize arginine to decrease the availability of this amino acid, which in turn (1) block the translation of CD3ζ, one of the important components of TCR complex; (2) inhibit T cell proliferation; and (3) promote T cell apoptosis [ 57 ]. We found that chronic alcohol consumption signifi cantly upregulates the expression of IL-4/IL-13 receptor α-chain (CD124) on MDSC [ 55 ], and decreases the concentration of arginine in the plasma of melanoma-bearing mice [ 35 ]. The increased MDSC could be associated with the inhibition of the memory and tumor-specifi c CD8 + T cell proliferation and dysfunction in the tumor-bearing mice.…”