A primer on tumour immunology and prostate cancer immunotherapy

Ren, Runhan; Koti, Madhuri; Hamilton, Thomas K.; Graham, Charles H.; Nayak, Jasmir G.; Singh, Jas; Drachenberg, Darrel

doi:10.5489/cuaj.3418

Cited by 11 publications

(8 citation statements)

References 57 publications

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“…Although recent years have seen great advances in treatments for prostate cancer, including second-line chemotherapy, anti-androgen therapies, and radiopharmaceuticals, none of these therapies are curative (13). Nonetheless, there is great potential for these and other existing therapies to be used synergistically with immunotherapies already present in clinical practice or in late stages of clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer

Mai

et al. 2016

Braz J Med Biol Res

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Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model. Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. Vaccination with the CTLA4-fused DNA not only induced a much higher level of anti-PSCA antibody, but also increased PSCA-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with PSCA-expressing tumors were generated. After injection of the tumor-bearing mouse model, the plasmid carrying the CTLA4 and PSCA fusion gene showed stronger inhibition of tumor growth than the plasmid expressing PSCA alone. These observations emphasize the potential of the CTLA4-fused DNA vaccine, which could represent a promising approach for tumor immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer

Mai

et al. 2016

Braz J Med Biol Res

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“…Given the strong correlation between the type, density, and spatial distribution of infiltrating lymphocytes and survival, there are therapeutic implications and support for immune therapies to enhance anti-tumor immune responses 49 , 50 . Immunotherapy, or the use of agents to recruit the host's immune system to target and destroy malignant cells, is particularly attractive for PCa.…”

Section: Introductionmentioning

confidence: 99%

“…Immunotherapy, or the use of agents to recruit the host's immune system to target and destroy malignant cells, is particularly attractive for PCa. This is because PCa has a relatively indolent rate of progression, which gives the immune system time to mount an effective, durable response, and the expression of tumor-specific antigens (i.e., prostate-specific antigen, prostate acid phosphatase, and prostate-specific membrane antigen) that could be targeted by immune modulators 49 , 51 , 52 . This therapeutic approach, termed “antigen-specific vaccination,” is promising, as evidenced by the success with Sipuleucel-T. Sipuleucel-T is an autologous vaccine derived from harvested mononuclear cells from the patient, incubated with recombinant prostatic acid phosphatase (PAP) antigen, and reinfused into the patient, leading to a PAP-specific CD4 + and CD8 + T-cell response 51 , 53 , 54 .…”

Section: Introductionmentioning

confidence: 99%

“…Responsiveness to therapy varied significantly based on age, variations in antibody titers, and clinicopathological features 53 , 54 , 56 . Various other types of vaccination approaches (e.g., vector-based vaccines, personalized peptide vaccination) and immunomodular therapies have been explored, although they remain in the early-to-mid stages of clinical investigation, and with mixed clinical results 49 , 57 . We and others in the field believe that development and validation of reliable methods to screen and select PCa patients for immunotherapy-based regimens, based on density, location, and quantity of clinically-relevant immune infiltrates in the prostate microenvironment, will support the use and effectiveness of this promising type of anti-cancer therapy 49 , 51 , 52 .…”

Section: Introductionmentioning

confidence: 99%

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Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer

et al. 2018

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Introduction: The androgen receptor (AR) regulates immune-related epithelial-to-mesenchymal transition (EMT), and prostate cancer (PCa) metastasis. Primary tumor-infiltrating lymphocytes (TILs) [CD3+, CD4+, and CD8+ TILs] are potential prognostic indicators in PCa, and variations may contribute to racial disparities in tumor biology and PCa outcomes.Aim: To assess the technical feasibility of tumor microarray (TMA)-based methods to perform multi-marker TIL profiling in primary resected PCa.Methods: Paraffin-embedded tissue cores of histopathologically-confirmed primary PCa (n = 40; 1 TMA tissue specimen loss) were arrayed in triplicate on TMAs. Expression profiles of AR, CD3+, CD4+, and CD8+ TILs in normal prostate, and the center and periphery of both the tumor-dominant nodule and highest Gleason grade were detected by IHC and associated with clinical and pathological data using standard statistical methodology. An independent pathologist, blinded to the clinical data, scored all samples (percent and intensity of positive cells).Results: TMAs were constructed from 21 (53.8%) Black and 18 (46.2%) White males with completely-resected, primarily pT2 stage PCa [pT2a (n = 3; 7.7%); pT2b (n = 2; 5.1%); pT2c (n = 27; 69.2%); pT3a (n = 5; 12.8%); mean pre-op PSA = 8.17 ng/ml]. The CD3, CD4, CD8, and CD8/CD3 cellular protein expression differed from normal in the periphery of the dominant nodule, the center of the highest Gleason grade, and the periphery of the highest Gleason grade (P < 0.05). Correlations between TIL expression in the center and periphery of the dominant nodule, with corresponding center and periphery of the highest Gleason grade, respectively, were robust, and the magnitude of these correlations differed markedly by race (P < 0.05).Conclusions: Multi-marker (AR, CD3, CD4, CD8) profiling with IHC analysis of TMAs consisting of primary, non-metastatic resected prostate cancer is technically feasible in this pilot study. Future studies will evaluate primary tumor immunoscore using semi-quantitative, IHC-based methodology to assess differences in the spectrum, quantity, and/or localization of TILs, and to gain insights into racial disparities in PCa tumor biology and clinical outcomes.

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“…Prostate cancer usually does not show any signs until it has progressed to an advanced stage. Prostate-specific antigen (PSA) has been used as a tumor marker for many years; however, the US Preventive Services Task Force (USPSTF) recommends against any routine PSA-based screening for prostate cancer [ 4 ]. Researchers pointed the possibility of overtreatment based on the aforementioned screening method with an increasing risk of side effects.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy as a Promising Treatment for Prostate Cancer: A Systematic Review

Janiczek

Szylberg

Kasperska

et al. 2017

Journal of Immunology Research

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Prostate cancer treatment is currently based on surgical removal, radiotherapy, and hormone therapy. In recent years, another therapeutic method has emerged—immunological treatment. Immunotherapy modulates and strengthens one's immune responses against cancer. Neoplastic cells naturally escape from the control of the immune system, and the main goal of immune therapy is to bring the control back. Satisfying outcomes after treatment of advanced melanoma and lung cancer suggest a great potential of immunotherapy as an approach for other tumors' treatment, especially in patients primarily introduced to palliative care. After initial clinical trials, immunotherapy seems to have different side effects than chemotherapy. Prostate cancer was the first neoplasm in which a specific vaccine significantly improved survival. There is a tremendous potential for synergistic combinations of immunotherapy with conventional cancer treatments. A combination of several drugs or methods can be a key in radical treatment of metastatic prostate cancer as demonstrated by preliminary studies.

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A primer on tumour immunology and prostate cancer immunotherapy

Abstract: No abstract

Cited by 11 publications

References 57 publications

Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer

Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer

Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer

Immunotherapy as a Promising Treatment for Prostate Cancer: A Systematic Review

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