Impact of aging on immune modulation by tumor

Tumor development and aging can each alter immune competence. The present s tudy aimed to determine the impact of Lewis lung carcinoma (LLC) presence o n immune parameters of middle-aged (averaging 6.5 months) versus aged (aver aging 21.3 months) mice. An a-e-associated decline in the CD4(+) cell frequ ency was seen in freshly isolated spleen and lymph node cells, as well as i n cultures stimulated with immobilized anti-CD3. This decline was not furth er exacerbated by tumor presence. What was prominently inhibited by tumor w as the capacity of either splenic or lymph node CD4(+) cells to become stim ulated to express IFN-gamma. Spleen and lymph node cultures from aged tumor -bearing mice had the lowest frequency of CD4(+)IFN-gamma (+) cells and the least amount of secreted IFN-gamma. CD8(+) cells were not affected by agin g, but tumor presence reduced the induction of CD8(+)IFN-gamma (+) cells in lymph node cultures. We previously showed that LLC growth stimulates myelo poiesis, as seen by splenomegaly and the mobilization of immune inhibitory CD34(+) progenitor cells. Tumor presence in middle-aged mice reduced spleen cell blastogenesis, which was mediated by CD34(+) cells. Aged mice had red uced blastogenesis, and this was further reduced by presence of tumor. Howe ver, neither the age-associated immune dysfunction nor the tumor-induced im mune suppression in aged mice was due to CD34(+) progenitor cells. These st udies show how tumor presence can further compromise the immune dysfunction that accompanies aging. In addition, they show that aging impacts on the m echanisms by which tumors inhibit T-cell capabilities, with myelopoiesis-as sociated CD34(+) cells mediating the immune depression of middle-aged tumor -bearers and an independent mechanism being responsible for the immune depr ession in aged tumor-bearing mice.