Chronic alcohol consumption decreases the percentage and number of NK cells in the peripheral lymph nodes and exacerbates B16BL6 melanoma metastasis into the draining lymph nodes

Abstract

NK cells in the lymph nodes play important roles in inhibiting tumor metastasis into draining lymph nodes. Previously, we reported that chronic alcohol consumption interferes with NK cell trafficking from the bone marrow to the spleen. Herein, we found that alcohol consumption decreases the numbers of NK cells in lymph nodes. Adoptive transfer experiments indicated that continued exposure of donor splenocytes to alcohol inhibits NK but not T cell trafficking to lymph nodes. Alcohol did not negatively affect CCR7 + and CXCR3 + NK cells, but decreased the percentage and number of CD62L + NK cells in the spleen, which are an important source of NK cell trafficking into the lymph nodes. These data suggest that modulation of the microenvironment associated with alcohol consumption impairs the trafficking of NK cells to lymph nodes. The decreased number of NK cells in the lymph nodes was associated with increased melanoma metastasis into the draining lymph nodes.

A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver

“…In the current study, 4 weeks of alcohol intake significantly decreased the numbers of NK cells and CD8 þ T cells and their ratios by 0.6-and 0.7-fold, respectively, in the peripheral blood (Fig. 4), which is consistent with previous studies (6,16). This result somewhat conflicts with above observation of NK cells' infiltration in liver, whereas the hepatic NK cells are also known as contributor in alcohol-induced liver injury (24).…”

“…Several epidemiologic studies presented controversial effects of alcohol consumption on cancer-associated outcomes, including survival rate and metastasis (5). An animal study showed chronic alcohol consumption accelerated melanoma metastasis into the lung by suppression of natural killer (NK) cells (6), whereas another study presented suppression of melanoma by alcohol intake via activating IFNg-producing immune cells (7).…”

Chronic Ethanol Feeding Induces Subset Loss and Hyporesponsiveness in Skin T Cells

“…First, the impact of chronic EtOH feeding upon LC and DETC proliferation rates was assessed by administering BrdU to mice in the appropriate drinking liquid (i.e., EtOH solution or water), followed by the analysis of BrdU incorporation in epidermal cell suspensions. Importantly, multiple studies have used similar BrdU administration methods to assess the effects of chronic EtOH feeding upon the proliferation rates of other hematopoietic cells (Zhang and Meadows, 2005, 2009; Zhang et al, 2011). EtOH feeding differentially impacted BrdU incorporation rates of LCs and DETCs, with a significant reduction occurring in the former population but not the latter (Fig.…”

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

“…NK cells play an important role in preventing B16 melanoma metastasis into lymph nodes [ 65 ]. We found that chronic alcohol consumption increases B16BL6 melanoma metastasis into the draining lymph nodes in mice bearing subcutaneous tumor [ 64 ].…”

“…Due to the decrease of bone marrow-derived mature NK cells, the portion of thymus-derived NK cells, which are a population of NK cells that express IL-7Rα (CD127) and produce large amount IFN-γ upon activation, is increased in the periphery [ 36 ]. Chronic alcohol consumption inhibits NK cell migration to lymph nodes through the downregulation of CD62L expression [ 64 ]. NK cells play an important role in preventing B16 melanoma metastasis into lymph nodes [ 65 ].…”