Lung cancers, like other malignancies, can escape immune recognition by downregulation of HLA class I molecules. Administration of IFN-gamma has been shown to upregulate HLA class I on NSCLC and thus may be a useful adjunct (37). Fas-ligand (Fas-L), frequently detected in lung carcinoma cell lines and resected tumors, can cause apoptosis of T cells. In fact, lung carcinoma cells were capable of killing the Fas-sensitive human T-cell line Jurkat in coculture experiments (65). Inhibiting Fas-L expression by tumors might therefore be a useful adjunct to immunotherapies. The tumor antigen RCAS1, positive in 47% of NSCLC specimens (and up to 80% of adenocarcinomas), induces apoptosis in immune cells bearing the RCAS1 receptor (66). Interference with its activity might improve the activity of lung cancer immunotherapy. Lung cancers may negatively regulate DC differentiation and this observation supports the use of ex vivo-generated DCs in vaccine strategies (67). Lung cancer cell lines express higher levels of proteins that can interfere with complement activity such as membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55), and CD59. Resistance to complement-mediated lysis of the lung cancer cell lines was much higher than that of normal cells (68). Inhibition of complement activity may allow lung cancers to avoid antibody-mediated cytotoxicity.
Inhibition of T-cell activity is also common in the setting of lung cancer. Woo observed high levels of CD4(+)CD25(+) regulatory T cells in lung cancers (69). These T cells mediate potent inhibition of autologous T-cell proliferation and suggest a mechanism whereby lung tumors may inhibit the host immune response (69). Monoclonal antibodies that can deplete CD25+ T cells may therefore be of use in inhibiting the counterregulatory response.
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