Human small cell lung carcinoma and carcinoid tumor regulate dendritic cell maturation and function

The induction of apoptosis In dendritic cells (DC) Is a key mechanism by wh ich tumors escape immune recognition and elimination. In fact, a number of studies have showed the correlation between the number of DC within the tum or and the clinical prognosis, suggesting that increased infiltration of tu mor tissue by DC was associated with better patient survival and low incide nce of metastatic disease. We compared the number of DC and their distribut ion pattern in human small-cell lung carcinoma and bronchial carcinoid tumo r (CT) tissues. Immunohistochemical analysis revealed the presence of cells expressing DC markers CD1a and CD83 in small-cell lung carcinoma tissues a nd the complete absence of these cells in CT samples. Next, we examined whe ther human lung tumor cells produce soluble factors that inhibit differenti ation of hematopoietic precursors into mature DC. The addition of small-cel l lung carcinoma-conditioned medium to CD34(+) precursor cell cultures sign ificantly inhibited colony-forming units of DC formation when compared with nontreated control DC cultures. Furthermore, DC generation and differentia tion was completely abrogated in CD34(+) cell cultures treated with CT-cond itioned medium, suggesting that CT-derived factors blocked CD34(+) cell dif ferentiation into DC or induced their apoptosis. Finally, now cytometry ana lysis of cultured DC confirmed these results. Thus, analysis of our data su ggests that human lung tumors produce factors that inhibit DC generation or maturation and may also induce apoptotic death of DC precursors in vitro.