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

Johnson LD, Nesslinger NJ, Blood PA, Chima N, Richier LR, Ludgate C, Pai HH, Lim JT, Nelson BH, Vlachaki MT, Lum JJ - Oncoimmunology (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Trev and Joyce Deeley Research Centre; Victoria, BC Canada.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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Figure 1: 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.

Mentions: We collected sera samples from a total of 56 patients with non-metastatic prostate cancer who were treated with ADT and EBRT. Since it was crucial to examine treatment-induced responses, patients were excluded if they received ADT prior to their first blood collection. In addition, some patients were lost to follow-up, leaving a small but well-controlled sample of 23 patients for further analysis (Table 1). To assess treatment-associated immune responses, patient sera were immunoblotted against whole cell lysates from the human prostate cancer cell line LNCaP as previously described.15 All results were confirmed by at least 2 independent immunoblots. Sera were scored as positive if they showed the appearance of 1 or more bands by western blotting either during treatment or within 1 y following. For all cases, we tested all available time points wherever possible. Seven of the 23 (30.4%) patients developed one or more seroreactivities. Of the 16 high-risk patients, 6 (37.5%) developed autoantibody responses, as did 1 (16%) of the intermediate-risk patients. The low-risk patient that was treated with ADT and EBRT did not develop an autoantibody response. In 4 of these patients (57.1%), new seroreactivity was observed after ADT but before EBRT. Figure 1 shows western blot results for 2 healthy donor controls (Fig. 1A), 1 representative patient who did not develop autoantibodies (Fig. 1B), and 2 representative patients who scored positive for treatment-associated autoantibodies (Fig. 1C and 1D).


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

Johnson LD, Nesslinger NJ, Blood PA, Chima N, Richier LR, Ludgate C, Pai HH, Lim JT, Nelson BH, Vlachaki MT, Lum JJ - Oncoimmunology (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125379&req=5

Figure 1: 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.
Mentions: We collected sera samples from a total of 56 patients with non-metastatic prostate cancer who were treated with ADT and EBRT. Since it was crucial to examine treatment-induced responses, patients were excluded if they received ADT prior to their first blood collection. In addition, some patients were lost to follow-up, leaving a small but well-controlled sample of 23 patients for further analysis (Table 1). To assess treatment-associated immune responses, patient sera were immunoblotted against whole cell lysates from the human prostate cancer cell line LNCaP as previously described.15 All results were confirmed by at least 2 independent immunoblots. Sera were scored as positive if they showed the appearance of 1 or more bands by western blotting either during treatment or within 1 y following. For all cases, we tested all available time points wherever possible. Seven of the 23 (30.4%) patients developed one or more seroreactivities. Of the 16 high-risk patients, 6 (37.5%) developed autoantibody responses, as did 1 (16%) of the intermediate-risk patients. The low-risk patient that was treated with ADT and EBRT did not develop an autoantibody response. In 4 of these patients (57.1%), new seroreactivity was observed after ADT but before EBRT. Figure 1 shows western blot results for 2 healthy donor controls (Fig. 1A), 1 representative patient who did not develop autoantibodies (Fig. 1B), and 2 representative patients who scored positive for treatment-associated autoantibodies (Fig. 1C and 1D).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Trev and Joyce Deeley Research Centre; Victoria, BC Canada.

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.

No MeSH data available.


Related in: MedlinePlus