Demystifying Immunotherapy in Prostate Cancer

Madan, Ravi A.; Gulley, James L.; Kantoff, Philip W.

doi:10.1097/ppo.0b013e31828160a9

Cited by 21 publications

(5 citation statements)

References 76 publications

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“…In the apoptotic aftermath of initial androgen deprivation therapy, leucocytes are further recruited to tumour tissue, but rather than reacting to the cancer, they may promote progression to CRPC (Luo et al , 2007 ; Ammirante et al , 2010 ). The field of immunotherapeutics seeks to exploit the potent and intact anti-tumour response and is reviewed in-depth elsewhere (Madan et al , 2013 ; Makkouk & Weiner, 2015 ; May et al , 2011 ). The most advanced clinical strategies for CRPC are therapeutic vaccines that induce a novel anti-tumour response, and immune checkpoint modulators that prevent suppression of the existing response.…”

Section: The Protective Role Of the Microenvironmentmentioning

confidence: 99%

Targeting the adaptive molecular landscape of castration‐resistant prostate cancer

2015

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Castration and androgen receptor (AR) pathway inhibitors induce profound and sustained responses in advanced prostate cancer. However, the inevitable recurrence is associated with reactivation of the AR and progression to a more aggressive phenotype termed castration-resistant prostate cancer (CRPC). AR reactivation can occur directly through genomic modification of the AR gene, or indirectly via co-factor and co-chaperone deregulation. This mechanistic heterogeneity is further complicated by the stress-driven induction of a myriad of overlapping cellular survival pathways. In this review, we describe the heterogeneous and evolvable molecular landscape of CRPC and explore recent successes and failures of therapeutic strategies designed to target AR reactivation and adaptive survival pathways. We also discuss exciting areas of burgeoning anti-tumour research, and their potential to improve the survival and management of patients with CRPC.

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Section: The Protective Role Of the Microenvironmentmentioning

confidence: 99%

Targeting the adaptive molecular landscape of castration‐resistant prostate cancer

2015

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“…Indeed, activation of inflammatory pathways have been linked to early carcinogenesis and progression (18–20). More recently novel strategies to harness the host immune response for therapeutic benefit are the focus of extensive preclinical and clinical research.…”

Section: Introductionmentioning

confidence: 99%

Consumption of Soy Isoflavone Enriched Bread in Men with Prostate Cancer Is Associated with Reduced Proinflammatory Cytokines and Immunosuppressive Cells

Lesinski

Reville²,

Mace³

et al. 2015

Cancer Prevention Research

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We hypothesized that soy phytochemicals may have immunomodulatory properties that may impact prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 prostate cancer patients with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to 2 slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on Day 56 versus baseline. Subgroup analysis indicated reduced Th1 (p=0.028) and MDSC-associated cytokines (p=0.035). Th2 and Th17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8+ or CD4+ T cells, but showed increased CD56+ NK cells (p=0.038). The percentage of cells with a T regulatory cell phenotype (CD4+CD25+FoxP3+) were significantly decreased after 56 days of soy bread (p=0.0136). Significantly decreased monocytic (CD33+HLADRnegCD14+) MDSC were observed in patients consuming soy bread (p=0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.

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“…Sipuleucel-T is thought to stimulate dendritic cells which in turn lead to activation of effector T-cells; producing an anti-tumor effect [76]. To ensure the quality of the immunotherapy product, it does undergo CD54+ testing prior to release.…”

Section: Antigen Specific Immunotherapiesmentioning

confidence: 99%

Immunotherapy for prostate cancer: recent developments and future challenges

Schweizer

Drake

2014

Cancer Metastasis Rev

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Since the approval of sipuleucel-T for men with metastatic castrate resistant prostate cancer in 2010, great strides in the development of anti-cancer immunotherapies have been made. Current drug development in this area has focused primarily on antigen specific [i.e. cancer vaccines and antibody based therapies)] or checkpoint inhibitor therapies, with the checkpoint inhibitors perhaps gaining the most attention as of late. Indeed, drugs blocking the inhibitory signal generated by the engagement of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) found on T-cells has emerged as potent means to combat the immunosuppressive milieu. The anti-CTLA-4 monoclonal antibody ipilimumab has already been approved in advanced melanoma and two phase III trials evaluating ipilimumab in men with metastatic castrate-resistant prostate cancer are underway. A phase III trial evaluating ProstVac-VF, a poxvirus-based therapeutic prostate cancer vaccine, is also underway. While there has been reason for encouragement over the past few years, many questions regarding the use of immunotherapies remain. Namely it is unclear what stage of disease is most likely to benefit from these approaches, how best to incorporate said treatments with each other and into our current treatment regimens and which therapy is most appropriate for which disease. Herein we review some of the recent advances in immunotherapy as related to the treatment of prostate cancer and outline some of the challenges that lie ahead.

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Demystifying Immunotherapy in Prostate Cancer

Cited by 21 publications

References 76 publications

Targeting the adaptive molecular landscape of castration‐resistant prostate cancer

Targeting the adaptive molecular landscape of castration‐resistant prostate cancer

Consumption of Soy Isoflavone Enriched Bread in Men with Prostate Cancer Is Associated with Reduced Proinflammatory Cytokines and Immunosuppressive Cells

Immunotherapy for prostate cancer: recent developments and future challenges

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