Role of Epigenetic Modification and Immunomodulation in a Murine Prostate Cancer Model

Sulek, Jay; Robinson, Samuel; Petrossian, Albert; Zhou, Shaoqiang; Goliadze, Ekaterine; Manjili, Masoud H.; Toor, Amir A.; Guruli, Georgi

doi:10.1002/pros.23275

Cited by 6 publications

(6 citation statements)

References 27 publications

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“…Epigenetic drugs might then result in making PCa cells more immunogenic and amenable to targeting by immune therapies. Similar results were obtained by Sulek et al [152], which additionally demonstrated that combining lenalidomide with decitabine induced dendritic cells activity and ability to stimulate T cells. Chemokines that attract effector and regulatory cells to the tumor are very relevant in regulating immune response.…”

Section: Role Of Immunoepigenetics?supporting

confidence: 88%

“…A summary of most recent studies addressing combination strategies between epigenetics and immune environment in PCa is depicted in Table 3 [108,[141][142][143][144][145][146][147][148][149][150][151][152]. Some studies have focused on epigenetic regulation of response to IFN, where both methylation and acetylation can be involved, as demonstrated by Dunn and collaborators [141].…”

Section: Role Of Immunoepigenetics?mentioning

confidence: 99%

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Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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In the last years, we have witnessed remarkable advances in targeted therapies for cancer patients. There is a growing effort to either replace or reduce the dose of unspecific, systemic (chemo)therapies, given the associated short- and long-term side effects, by introducing more specific targeted therapies as single or combination agents. Due to the well-known implications of the immune system and epigenetic landscape in modulating cancer development, both have been explored as potential targets in several malignancies, including those affecting the genitourinary tract. As the immune system function is also epigenetically regulated, there is rationale for combining both strategies. However, this is still rather underexplored, namely in urological tumors. We aim to briefly review the use of immune therapies in prostate, kidney, bladder, and testicular cancer, and further describe studies providing supporting evidence on their combination with epigenetic-based therapies.

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Section: Role Of Immunoepigenetics?supporting

confidence: 88%

Section: Role Of Immunoepigenetics?mentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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“…Here, a broad range of tumorassociated antigens, such as CEA, MUC1 and PSA, was observed and an association with augmented expression of multiple proteins involved in antigen processing and tumor immune recognition was found (83). Especially in prostate cancer, decreased expression of CTAs has been discovered as a means of escaping immune monitoring, with several studies addressing the role of HDACis and DNMTis (e.g., azacytidine) in increasing tumor immunogenicity (84,85). Although induction of CTAs by azacytidine and trichostatin A was also observed for bladder cancer (86,87), our research did not yield further results regarding immunomodulation through epigenetic therapy in bladder cancer.…”

Section: Epigenetic Immunomodulation In Urological Tumorsmentioning

confidence: 97%

Tumor immunotherapy—the potential of epigenetic drugs to overcome resistance

Grunewald¹,

Schulz²,

Skowron³

et al. 2018

Transl. Cancer Res

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Immune checkpoint inhibitors recently introduced into clinical practice have enriched available treatment options for a number of solid cancers. The efficacy of these treatments may however be impaired by tumor cell-intrinsic factors and tumor cell-extrinsic factors resulting in repressed tumor immunogenicity and host immune response. Accordingly, only a subgroup of patients responds to this treatment. Epigenetic drugs may offer an exciting novel approach to reverse immune suppression and to 'prime' tumors for immunotherapy, as DNA methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors and bromodomain and extra-terminal motif (BET) inhibitors show immunomodulatory properties by affecting both cancer cells directly as well as the tumor microenvironment. Upregulation of tumor associated antigens (TAAs), ligands for natural killer (NK) cell receptors, chemokine expression, altered immune checkpoint molecules, antigen procession and presentation as well as induction of viral mimicry improve recognition of cancer cells. In the tumor microenvironment, suppression of myeloid-derived suppressor cells (MDSCs), modulation of regulatory T cells function and activation of NK cells may improve immunogenic efficacy. In conclusion, current preclinical data supports translation of combinatorial treatment approaches into clinical trials and practice.

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“…Therefore, improving the immunogenicity of cancer is essential to improving cancer immunotherapy. Epigenetic modulators such as azacytidine (Aza) and decitabine (Dec) function as cytosine analogs, which lead to their incorporation into newly synthesized DNA strands during S phase of the cell cycle; these agents have been shown to enhance immunogenicity of tumor cells by inducing the expression of a panel of highly immunogenic cancer testis antigens (CTAs), and result in improved immunotherapy of cancer [51,52]. Both Aza and Dec also induce the expression of tumor suppressor gene p53 [53] and the death receptor Fas [54] on tumor cells.…”

Section: Epigenetic Targeting Of Tumor Cells For Immune Modulationmentioning

confidence: 99%

Conditioning neoadjuvant therapies for improved immunotherapy of cancer

Benson

Manjili

Habibi

et al. 2017

Biochemical Pharmacology

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Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy. To this end, low dose immunogenic chemotherapies, epigenetic modulators and inhibitors of cell cycle progression are potential candidates for rendering tumors highly responsive to immunotherapy. Next generation immunotherapeutics are therefore predicted to be highly effective against cancer, when they are used following appropriate immune modulatory compounds or targeted delivery of tumor cell cycle inhibitors using nanotechnology.

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Role of Epigenetic Modification and Immunomodulation in a Murine Prostate Cancer Model

Cited by 6 publications

References 27 publications

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Tumor immunotherapy—the potential of epigenetic drugs to overcome resistance

Conditioning neoadjuvant therapies for improved immunotherapy of cancer

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