Evaluation of the humoral immune response against survivin in patients with lung cancer

Abstract

DedicationTo my mother, the source of inspiration, the eternal flame and support, I would like to dedicate this effort and to tell her if it wasn't for you I might have give up before I achieved the goal of my life.To my late father, the hero who put my feet on the track of education and offered a helping hand whenever I tripped on my first step, but did not live long enough to see me achieve my goals, I say: I'm there father, I love you and I wish you were here to see your dreams come true! God bless you. SummaryAutoantibodies have been shown to be present in the circulation of people with various forms of solid tumours before cancer-associated antigens can be detected. Unlike circulating proteins that are shed by bulky tumors, autoantibodies are detectable even when antigen expression is minimal and they can be measured up to 5 years prior to disease detection. They are usually directed against oncoproteins, aberrantly expressed tumour suppression genes, proliferation-associated antigens as well as nuclear antigens.Existing evidence regarding spontaneous anti-survivin humoral responses in lung cancer is inconclusive. Moreover, despite that cancer cell death elicited by radiotherapy and some chemotherapeutic agents seems to be immunogenic, information about the possible effect of treatment on these responses, is lacking. Serum samples from 33 small cell lung cancer (SCLC) and 117 non-small cell lung cancer (NSCLC) patients upon diagnosis, and from 100 controls, were tested by ELISA for anti-survivin antibodies. Cutoff was set to the mean+2SD of controls. 7.7% of NSCLC, none of the SCLC patients and 2% of the controls appeared with elevated antibody levels (OR 3.6, 95% CI 0.7-17.3 for NSCLC, OR 0.6, 95% CI 0.03-12.6 for SCLC). Measurement of antibodies in 76 NCSLC patients post therapies and during their follow-up, revealed 12 NSCLC patients that increased their antibody levels up to 2-38 times, and 7 others that decreased them by 2-8 times. No significant correlation was uncovered between either the antibody levels upon diagnosis or their changes post therapies and during follow-up, and any clinicopathological parameter, their response to treatment and survival. We conclude that survivin does not induce considerable humoral responses in lung cancer. Potentially, however, strong anti-survivin antibody responses can be elicited during the follow-up of the patients, whose clinical significance remains to be elucidated. These findings, together with our previous data concerning survivin expression and the related cytolytic T cell responses in lung cancer, signify a high tolerogenic potential of this tumor-associated antigen.