Impact of androgen-deprivation therapy on the immune system: implications for combination therapy of prostate cancer

Aragon‐Ching, Jeanny B.; Williams, Kirsten M.; Gulley, James L.

doi:10.2741/2441

Cited by 128 publications

(95 citation statements)

References 92 publications

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“…As reviewed by Aragon-Ching et al (32), phase I and phase II trials indicated that androgen ablation may boost immune responses elicited by DCs, allogeneic prostate cancer cell lysate, or GM-CSF-secreting tumor cell-based vaccines (88). Arlen et al (89) were the first to conduct a randomized study evaluating the use of vaccine alone versus concomitant vaccine plus weekly administration of docetaxel and steroids, with the end points of monitoring immune responses in 28 patients bearing a metastatic, androgen-resistant prostate cancer.…”

Section: Figurementioning

confidence: 99%

“…The influence of androgens on lymphocyte development and activation has been reviewed (32). Experimental data indicate that androgen deprivation increases the number of naive T cells exported from the thymus and may therefore contribute to broadening the repertoire of T cell immunity, leading to effective antitumor immune responses and breaking of tumor-induced tolerance (33,34).…”

Section: Immunostimulatory Side Effects Of Anticancer Drugsmentioning

confidence: 99%

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The anticancer immune response: indispensable for therapeutic success?

Apétoh²,

et al. 2008

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Although the impact of tumor immunology on the clinical management of most cancers is still negligible, there is increasing evidence that anticancer immune responses may contribute to the control of cancer after conventional chemotherapy. Thus, radiotherapy and some chemotherapeutic agents, in particular anthracyclines, can induce specific immune responses that result either in immunogenic cancer cell death or in immunostimulatory side effects. This anticancer immune response then helps to eliminate residual cancer cells (those that fail to be killed by chemotherapy) or maintains micrometastases in a stage of dormancy. Based on these premises, in this Review we address the question, How may it be possible to ameliorate conventional therapies by stimulating the anticancer immune response? Moreover, we discuss the rationale of clinical trials to evaluate and eventually increase the contribution of antitumor immune responses to the therapeutic management of neoplasia.Nonstandard abbreviations used: ACT, adoptive cell transfer; ATM, ataxia telangiectasia mutated; CEA, carcinoembryonic antigen; CHK1, checkpoint kinase-1; CRT, calreticulin; 5-FU, 5-fluorouracil; HMGB1, high mobility group box 1 protein; IM, imatinib mesylate; KLH, keyhole limpet hemocyanin; NKG2D, NK cell group 2D; PSA, prostate-specific antigen; TRP-2, tyrosinase-related protein 2.

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Section: Figurementioning

confidence: 99%

Section: Immunostimulatory Side Effects Of Anticancer Drugsmentioning

confidence: 99%

The anticancer immune response: indispensable for therapeutic success?

Apétoh²,

et al. 2008

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“…Following a phase I trial of Adv-tk in men with locally recurrent prostate cancer showing its safety and trial data demonstrating a significant increase in PSA doubling time (PSADT) (from 15.9 to 42.5 months; P= 0.0271) [18,19], a phase II trial was conducted in men with newly diagnosed localized intermediate and high-risk prostate cancer receiving radiation and androgen deprivation therapy (ADT). Adv-tk was studied in this setting because both radiation and ADT have been shown to have the potential to enhance anti-tumor immune responses [20][21][22][23][24][25][26]. In this phase II trial men receiving radiation, ADT and Adv-tk showed sustained T cell immune responses at a year.…”

Section: Prostatakmentioning

confidence: 96%

“…ADT has been found to potentiate an immune response through a number of mechanisms including increasing T cell infiltration into the prostate, increasing thymic production of naïve T cells, and diminishing immune tolerance [23][24][25][26]. Preclinical studies of enzalutamide and abiraterone have found that these agents enhance immune responses and lead to improved outcomes in combination with immunotherapy [69,70].…”

Section: Future Directionsmentioning

confidence: 97%

Integrating Immunotherapies in Prostate Cancer

Strauss

Madan

2015

Curr Oncol Rep

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In recent years, immunotherapy has emerged as a viable and promising treatment for prostate cancer. Beyond sipulecuel-T, phase III trials are evaluating multiple vaccine and immune-based therapies in men with this disease. Evidence suggests that many of these therapies are effective at augmenting immune responses and slowing tumor growth rates. Yet prospective data evaluating these responses as surrogates for survival are still needed. In the absence of validated intermediate markers of response, growing data suggests that patients with more indolent disease are more likely to benefit from immunotherapies. In order to further optimize immunotherapy use, ongoing trials are evaluating its combination with traditional as well as other immune-based treatments. Preliminary data from these trials are promising and are shedding new light on this area.

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“…Treatment of the patients with 3 to 4 months of an LHRH-a immediately prior to sipuleucel-T treatment may have contributed to the observed prolongation of PSADT in the treatment arm. Recent studies suggest a potential synergy between androgen deprivation and immunotherapy (34). Specifically, castration or androgen deprivation therapy has been shown to induce Time from randomization (months) 48 60…”

Section: Discussionmentioning

confidence: 99%

Randomized Trial of Autologous Cellular Immunotherapy with Sipuleucel-T in Androgen-Dependent Prostate Cancer

Beer

Bernstein

Corman

et al. 2011

Clinical Cancer Research

123

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Purpose: Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC).Experimental Design: Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n ¼ 117) or control (n ¼ 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated.Results: Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR ¼ 0.936, P ¼ 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P ¼ 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR ¼ 0.728, P ¼ 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization.Conclusions: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated. Clin Cancer Res; 17(13); 4558-67. Ó2011 AACR.

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Impact of androgen-deprivation therapy on the immune system: implications for combination therapy of prostate cancer

Cited by 128 publications

References 92 publications

The anticancer immune response: indispensable for therapeutic success?

The anticancer immune response: indispensable for therapeutic success?

Integrating Immunotherapies in Prostate Cancer

Randomized Trial of Autologous Cellular Immunotherapy with Sipuleucel-T in Androgen-Dependent Prostate Cancer

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