Antibodies against autologous tumor cell proteins in patients with small-cell lung cancer: Association with improved survival

Background: The frequency and clinical relevance of human anti-tumor immune responses is not well known, and few target antigens have been identified. Purpose: This study was designed to determine the frequency of antibodies reactive against extracts of autologous tumor cell lines and to correlate these data with survival. Methods: Serum samples were obtained from 40 lung cancer patients treated on National Cancer Institute protocols. These sera were used as probes in immunoblots against protein extracts from tumor cell lines derived from each of these patients. Results: We detected serum antibodies against autologous tumor cell proteins in 21 (58%) of the 36 patients with small-cell lung cancer (SCLC) and three (75%) of the four with non-small-cell lung cancer (NSCLC). Two patients' sera detected the p53 tumor suppressor gene product and two detected the product of the HuD gene (associated with paraneoplastic neurological syndromes) in their autologous tumor cell lysates. SCLC patients with antibodies against autologous tumor cell proteins had improved survivals compared with those in the antibody-negative group (P =.059). All patients who lived longer than 36 weeks were antitumor antibody positive. Sera from six (86%) of seven patients with limited disease were positive for antibodies that reacted against autologous tumor cells, compared with 15 of 29 (52%) of sera from patients with extensive disease. Conclusions: Our results suggest that the sera from patients with SCLC frequently contain antibodies against tumor cell proteins and that these antibodies are associated with improved survival. Implications: These data suggest that an antitumor immune response may affect tumor growth, and that the anonymous proteins detected by antitumor antibodies in lung cancer patient sera may represent proteins involved in the development of lung cancer or in its clinical manifestations. [J Natl Cancer Inst 85:2012-2018, 1993]