Beyond the Immune Suppression: The Immunotherapy in Prostate Cancer

Silvestri, Ida; Cattarino, Susanna; Aglianò, Anna Maria; Collalti, Giulia; Sciarra, Alessandro

doi:10.1155/2015/794968

Cited by 19 publications

(16 citation statements)

References 91 publications

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“…There are several viable ways to induce an immune response against TAAs, in part determined by whether the antigens are localized intra- or extracellularly. For instance, although chimeric antigen receptors ( 1 , 2 ) and bispecific antibodies crosslinking cytotoxic T cells with cancer cells ( 3 ) rely on the antigens’ cell surface presence, ectopic T cell receptor ( 4 ), tumor-infiltrating lymphocyte (TIL) ( 5 , 6 ), and vaccine-based approaches ( 7 – 18 ) require display of antigenic peptides by major histocompatibility complexes (MHCs), regardless of whether the peptides represent intra- or extracellular TAAs.…”

Section: Introductionmentioning

confidence: 99%

SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes

Lacher¹,

Bauer

Fury

et al. 2018

Front. Immunol.

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Targeted cancer immunotherapy with irradiated, granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting, allogeneic cancer cell lines has been an effective approach to reduce tumor burden in several patients. It is generally assumed that to be effective, these cell lines need to express immunogenic antigens coexpressed in patient tumor cells, and antigen-presenting cells need to take up such antigens then present them to patient T cells. We have previously reported that, in a phase I pilot study ( NCT00095862), a subject with stage IV breast cancer experienced substantial regression of breast, lung, and brain lesions following inoculation with clinical formulations of SV-BR-1-GM, a GM-CSF-secreting breast tumor cell line. To identify diagnostic features permitting the prospective identification of patients likely to benefit from SV-BR-1-GM, we conducted a molecular analysis of the SV-BR-1-GM cell line and of patient-derived blood, as well as a tumor specimen. Compared to normal human breast cells, SV-BR-1-GM cells overexpress genes encoding tumor-associated antigens (TAAs) such as PRAME, a cancer/testis antigen. Curiously, despite its presumptive breast epithelial origin, the cell line expresses major histocompatibility complex (MHC) class II genes (HLA-DRA, HLA-DRB3, HLA-DMA, HLA-DMB), in addition to several other factors known to play immunostimulatory roles. These factors include MHC class I components (B2M, HLA-A, HLA-B), ADA (encoding adenosine deaminase), ADGRE5 (CD97), CD58 (LFA3), CD74 (encoding invariant chain and CLIP), CD83, CXCL8 (IL8), CXCL16, HLA-F, IL6, IL18, and KITLG. Moreover, both SV-BR-1-GM cells and the responding study subject carried an HLA-DRB3*02:02 allele, raising the question of whether SV-BR-1-GM cells can directly present endogenous antigens to T cells, thereby inducing a tumor-directed immune response. In support of this, SV-BR-1-GM cells (which also carry the HLA-DRB3*01:01 allele) treated with yellow fever virus (YFV) envelope (Env) 43–59 peptides reactivated YFV-DRB3*01:01-specific CD4+ T cells. Thus, the partial HLA allele match between SV-BR-1-GM and the clinical responder might have enabled patient T lymphocytes to directly recognize SV-BR-1-GM TAAs as presented on SV-BR-1-GM MHCs. Taken together, our findings are consistent with a potentially unique mechanism of action by which SV-BR-1-GM cells can act as APCs for previously primed CD4+ T cells.

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Section: Introductionmentioning

confidence: 99%

SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes

Lacher¹,

Bauer

Fury

et al. 2018

Front. Immunol.

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“…Surgery and chemotherapy are the main treatment strategies for prostate cancer (2)(3)(4). Due to the malignant migration and invasion potential of human prostate cancer cells, the current therapy for this type of cancer remains unsatisfactory (5).…”

Section: Introductionmentioning

confidence: 99%

miR‑20b promotes cellular proliferation and migration by directly regulating phosphatase and tensin homolog in prostate cancer

Guo

Xiao

et al. 2017

Oncol Lett

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Abstract. MicroRNAs are small non-coding RNAs, which are critical regulators of carcinogenesis and tumor progression. Previous studies have identified that microRNA-20b (miR-20b) acts as an oncogene in numerous cancers. However, the role of miR-20b in prostate cancer remains unclear. The present study aimed to investigate the expression of miR-20b in prostate cancer and to examine whether modulating miR-20b expression impacts prostate cancer cellular proliferation and migration. It was revealed that miR-20b was strongly expressed in prostate cancer tissues compared with adjacent normal prostate tissues (P<0.05). Knockdown of miR-20b expression by miR-20b inhibitor inhibited VCaP and PC-3 cell growth and migration. Through bioinformatics analysis, phosphatase and tensin homolog (PTEN) was predicted as a target gene of miR-20b in prostate cancer cells, which was validated by dual-luciferase reporter assay and western blot analysis. In addition, restoration of PTEN expression levels did not affect endogenous miR-20b expression in prostate cancer cells. In conclusion, the present study indicated that miR-20b promotes cellular proliferation and migration by directly regulating PTEN in prostate cancer.

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“… 1 In the USA alone, the estimated yearly new cases of prostate cancer were over 220,000 and the estimated yearly death from prostate cancer was over 25,000 in 2015. 1 While patients with prostate cancer may be treated with several efficient therapies, including immunotherapy, 2 radiation therapy, 3 or surgery, 4 understanding the molecular mechanisms of human prostate cancer, developing early diagnostic methods or noninvasive focal therapies for patients with prostate cancer are still the greatest challenge ahead.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-125a-5p regulates cancer cell proliferation and migration through NAIF1 in prostate carcinoma

Cao

2015

OTT

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BackgroundWe investigated the functional roles of microRNA-125a-5p in regulating human prostate carcinoma.MethodsQuantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to evaluate the gene expression levels of miR-125a-5p in eight prostate cancer cell lines and nine biopsy specimens from patients with prostate cancer. miR-125a-5p was genetically knocked down in prostate cancer cell lines, DU145 and VCaP cells by lentiviral transduction. The effects of miR-125a-5p downregulation on prostate cancer cell proliferation and migration were evaluated by MTT assay and transwell assay, respectively. Direct regulation of miR-125a-5p on its downstream targets, NAIF1, and apoptotic gene caspase-3 were evaluated through dual-luciferase reporter assay, qRT-PCR, and Western blot, respectively. NAIF1 was then ectopically overexpressed in DU145 and VCaP cells to modulate prostate cancer cell proliferation and migration. Finally, the effects of miR-125a-5p downregulation or NAIF1 overexpression on the growth of in vivo prostate cancer xenograft were evaluated.ResultsmiR-125a-5p was upregulated in prostate cancer cell lines and human prostate carcinomas. Lentivirus induced miR-125a-5p downregulation in DU145 and VCaP cells inhibited prostate cancer cell proliferation or migration. NAIF1 was the direct target of miR-125a-5p, as both gene and protein expression levels of NAIF1, as well as caspase-3 were upregulated by miR-125a-5p. Forced overexpression of NAIF1 had similar antitumor effects as miR-125a-5p downregulation on prostate cancer cell proliferation and migration. In vivo prostate xenograft assay confirmed the tumor-suppressive effect of miR-125a-5p downregulation or NAIF1 overexpression.ConclusionmiR-125a-5p regulates prostate cancer cell proliferation and migration through NAIF1.

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Beyond the Immune Suppression: The Immunotherapy in Prostate Cancer

Cited by 19 publications

References 91 publications

SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes

SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes

miR‑20b promotes cellular proliferation and migration by directly regulating phosphatase and tensin homolog in prostate cancer

MicroRNA-125a-5p regulates cancer cell proliferation and migration through NAIF1 in prostate carcinoma

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