Immunotherapy for Prostate Cancer: Where We Are Headed

Schepisi, Giuseppe; Farolfi, Alberto; Conteduca, Vincenza; Martignano, Filippo; Lisi, Delia De; Ravaglia, Giorgia; Rossi, Lorena; Menna, Cecilia; Bellia, S.R.; Barone, Domenico; Gunelli, Roberta; Giorgi, Ugo De

doi:10.3390/ijms18122627

Cited by 47 publications

(39 citation statements)

References 53 publications

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“…Since then, several vaccine-based therapies have demonstrated promising results, and seem to especially benefit patients with a good prognostic disease and low disease burden (for extended review refer to [127]). With the advent of checkpoint inhibitors these agents were also tested in PCa [128]. These agents do not elicit a specific response against an individual target (contrarily to therapeutic vaccines) and, until now, they have not yet demonstrated convincing overall survival benefits in PCa patients.…”

Section: Immune Therapies-brief Overview In Prostate Cancermentioning

confidence: 99%

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: Immune Therapies-brief Overview In Prostate Cancermentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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“…23 Checkpoint inhibitors have shown limited efficacy so far, which might be related to the low mutational load in this tumor. 24,25 A randomized phase III trial was performed in patients with metastatic, castration resistant prostate cancer for testing RT only (8 Gy in one fraction to 1-5 bone metastases) versus RT followed by Ipilimumab treatment. Although the trial did not meet the primary endpoint of significantly improved overall survival, disease-free survival was prolonged, and an overall survival benefit was observed in the subgroup of patients with favourable prognostic factors.…”

Section: Introductionmentioning

confidence: 99%

Impact of curative radiotherapy on the immune status of patients with localized prostate cancer

et al. 2018

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Combination of radiotherapy with immunotherapy has become an attractive concept for the treatment of cancer. The objective of this study was to assess the effect of curative, normofractionated radiotherapy on peripheral immune lymphocytes in prostate cancer patients, in order to propose a rationale for scheduling of normofractionated radiotherapy with T-cell based immunotherapy. In a prospective study (clinicaltrials.gov: NCT01376674), eighteen patients with localized prostate cancer were treated with radiotherapy with or without hormonal therapy. Irradiation volumes encompassed prostate and, in select cases, elective pelvic nodal regions. Blood samples were collected from all patients before, during, and after radiotherapy, as well as from 6 healthy individuals as control. Normofractionated radiotherapy of prostate cancer over eight weeks had a significant influence on the systemic immune status of patients compared to healthy controls. Absolute leukocyte and lymphocyte counts decreased during treatment as did peripheral blood immune subsets (T cells, CD8 + and naïve CD4 + T cells, B cells). Regulatory T cells and NK cells increased. Proliferation of all immune cells except regulatory T cells increased during RT. Most of these changes were transient. Importantly, the functionality of T lymphocytes and the frequency of antigen-specific CD8 + T cells were not affected during therapy. Our data indicate that combination of normofractionated radiotherapy with immunotherapy might be feasible for patients with prostate cancer. Conceptually, beginning with immunotherapy early during the course of radiotherapy could be beneficial, as the percentage of T cells is highest, the percentage of regulatory T cells is lowest, and as the effects of radiotherapy did not completely subside 3 months after end of radiotherapy.

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“…Nonetheless, the documented survival benefit associated with sipuleucel-T in the IMPACT trial has paved the way towards a number of trials assessing the efficacy and safety of cancer vaccines, used as monotherapy or in combination with other drugs with potential anticancer activity [ 81 ]. Among the agents tested in mCRPC, it is worth mentioning PROSTVAC-VF, GVAX, and DCVAC/PCa.…”

Section: Prostate Cancer Vaccinesmentioning

confidence: 99%

Is There a Role for Immunotherapy in Prostate Cancer?

Rizzo

Mollica

Cimadamore

et al. 2020

Cells

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In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials assessing programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors have shown limited benefits. Moreover, despite sipuleucel-T representing the only cancer vaccine approved by the Food and Drug Administration (FDA) for mCRPC following the results of the IMPACT trial, the use of this agent is relatively limited in everyday clinical practice. The identification of specific histological and molecular biomarkers that could predict response to immunotherapy represents one of the current challenges, with an aim to detect subgroups of mCRPC patients who may benefit from immune checkpoint monoclonal antibodies as monotherapy or in combination with other anticancer agents. Several unanswered questions remain, including the following: is there—or will there ever be—a role for immunotherapy in prostate cancer? In this review, we aim at underlining the failures and promises of immunotherapy in prostate cancer, summarizing the current state of art regarding cancer vaccines and immune checkpoint monoclonal antibodies, and discussing future research directions in this immunologically “cold” malignancy.

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Immunotherapy for Prostate Cancer: Where We Are Headed

Cited by 47 publications

References 53 publications

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Impact of curative radiotherapy on the immune status of patients with localized prostate cancer

Is There a Role for Immunotherapy in Prostate Cancer?

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