Tumor-associated autoantibodies correlate with poor outcome in prostate cancer patients treated with androgen deprivation and external beam radiation therapy

Abstract

Standard cancer treatments trigger immune responses that may influence tumor control. The nature of these responses varies depending on the tumor and the treatment modality. We previously reported that radiation and androgen-deprivation therapy (ADT) induce tumor-associated autoantibody responses in prostate cancer patients. This follow-up analysis was conducted to assess the relationship between autoantibody responses and clinical outcome. Patients with non-metastatic prostate cancer received external beam radiation therapy (EBRT) plus neoadjuvant and concurrent androgen deprivation. Treatment-induced autoantibodies were detected in almost a third of patients receiving combinatorial ADT and EBRT. Unexpectedly, patients that developed autoantibody responses to tumor antigens had a significantly lower 5-year biochemical failure-free survival (BFFS) than patients that did not develop an autoantibody response. Thus, tumor-reactive autoantibodies may be associated with increased risk of biochemical failure and immunomodulation to prevent autoantibody development may improve BFFS for select, high-risk prostate cancer patients receiving both ADT and EBRT.

Keywords: androgen deprivation therapy; biochemical failure; external beam radiation therapy; prostate cancer; tumor-associated autoantibody.

Figure 1. Treatment-associated responses to prostate tumor antigens. Western blot analysis of serum from 2 healthy donor controls and 3 patients with prostate cancer probed against LNCaP cell lysate. The timing of sample collection for each patient is indicated. New seroreactivities are indicated with arrows. (A) Two healthy donor controls showing no seroreactivity. (B) Patient 052, who did not develop an autoantibody response throughout treatment. (C) Patient 054, who was treated with androgen-deprivation therapy (ADT) plus external beam radiation therapy (EBRT) and developed a new response 8 mo post-EBRT. (D) Patient 170, who developed two new responses 1 mo post-EBRT. Each blot was re-probed with actin without the multichannel device to ensure equal protein loading across each lane. The lines indicate the original slot-blot lane for each sample.

Figure 2. Treatment-associated autoantibody responses correlate with increased likelihood of biochemical failure. Kaplan-Meier analysis of biochemical failure-free survival according to development of an autoantibody response. Sera from prostate cancer patients (n = 23) receiving androgen-deprivation and external beam radiation bimodal therapy were evaluated for the presence of autoreactive antibodies and plotted according to biochemical failure, as indicated by elevated prostate specific antigen (PSA). Autoantibody-positive subjects are indicated with a solid line and autoantibody-negative subjects are indicated with a dashed line. Check marks indicate censored subjects. A log-rank test was performed to determine the P value.