Despite immune defects, antitumor immune responses can be detected in some lung cancer patients. For example, more than half of SCLC and NSCLC patients have been described to have circulating antibodies reactive with autologous tumor proteins (9). Presence of these antibodies predicts better response to therapy and survival in some studies (9-11), whereas others, such as those specific for p53, are associated with a survival effect in some but not other studies (12-20). Detecting in vivo antigen-specific T-cell responses in lung cancer patients has been more challenging. Lymphocytes from regional lymph nodes draining lung cancers proliferate in response to autologous tumor to a greater extent than do peripheral blood lymphocytes (8,21), suggesting enrichment for tumor-specific effectors in regional lymph nodes. Tumor-infiltrating lymphocytes from lung cancers have been discovered to have a restricted T-cell receptor V-beta usage (22), a marker for the oligoclonality expected with an antigen-specific immune response. Cytotoxic T lymphocytes (CTLs) that can recognize autologous tumor have also been identified in lung cancer patients (23). T cells specific for the tumor antigen HER2/neu have been identified in patients with NSCLC (24). Finally, it has been possible to activate tumor antigen-specific T cells from lymphocytes obtained from peripheral blood, tumor specimens, or regional lymph node lymphocytes of healthy volunteers and lung cancer patients (25-27).
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