Caffeic acid restores the M1-polarized immune balance but decreases IgG and IgM levels in human colorectal cancer HT-29 cell-bearing nude mice

Caffeic acid (CA) has been found to have the potential to inhibit the growth of human colorectal cancer HT-29 cells <i>in vitro</i>. However, the effects of CA administration on colorectal cancer growth and immunity <i>in vivo</i> remain unclear. To unravel the mystery of CA administration on cancer cell growth, serum antibody titers, lymphoid lineage cells in the peripheral blood, and the M1/M2 immune balance in BALB/c nude mice subcutaneously loaded with human colorectal cancer HT-29 cells for 35 days were examined in the experiment. The experimental mice were respectively given low (6 mg CA per kg AIN-93M feed), medium (30 mg CA per kg AIN-93M feed), and high (60 mg CA per kg AIN-93M feed) doses for 35 days. The results showed that CA administration tended to decrease the cancer cell volume and serum IgG and IgM levels compared to those in the dietary control (DC) group. CA administration slightly increased the proportion of CD3⁺ T and CD49⁺ natural killer cells, but decreased CD19⁺ B cells in the peripheral blood compared to those in the DC group, causing the immune cell distribution to be closer to the vehicle control (VC) group. The HT-29 cell-bearing mice exhibited an M2-polarized immune balance based on the TNF-α (M1)/IL-10 (M2) cytokine secretion ratio by macrophages compared to that in the VC group. Notably, low-dose CA administration significantly (<i>P</i> < 0.05) increased the TNF-α/IL-10 cytokine secretion ratio compared to that in the DC group, evidencing that low-dose CA administration reversed the immune response toward the M1-polarized immune balance in the HT-29 cell-bearing mice. CA administration may restore the M1-polarized immune balance but decrease serum IgG and IgM levels in subjects with colorectal cancer cells.