PD-L1, Prostate Cancer
Conditions
Brief summary
Immunotherapy is currently revolutionizing the field in oncology. However, prostate cancer until now fails to respond to classical IO, like PD-1 and CTLA-4 inhibitors. Radiotherapy (RT) delivered to the primary tumor impacts both tumor cells and surrounding stromal cells. Radiation damage to cancer cells exposes tumor-specific antigens leading to increased visibility to the immune system by improved priming and activation of cytotoxic T cells. RT-induced modulation of the tumor microenvironment may also facilitate the recruitment and infiltration of immune cells by increasing the expression or T-cell attracting chemokines and by increasing T-cell docking molecules on the endothelial cells like VCAM-1. The main-hypothesis is that HDR-brachytherapy will turn an immunologically cold (no T-cell infiltrations) prostate cancer into an immunologically hot (CD4 and CD8-cell infiltrations) tumor, creating leverage points for different forms of IO.
Detailed description
Prospective analysis of biopsies from 10 patients with local recurrence in the prostate selected for salvage HDR brachytherapy in MAASTRO Clinic, Maastricht. HDR treatment is standard in Maastro Clinic for local relapses of prostate cancer after previously irradiation (internal or external). Biopsies will be taken at 4 different time points (before and after the 1st fraction; before the 2nd and 3rd fraction of the salvage treatment). Several immunotyping (expression of PD-(L)-1, CXCL12, IL-23 receptor, etc.) and HLA class I expression will be performed on the biopsies. In addition, HLA genotypes will be determined on DNA isolated from pheripheral blood. The plasma and the biopsies will be stored for eventually additional research.
Interventions
RADIATIONHDR salvage brachytherapy
In patients receiving HDR salvage brachytherapy for locally relapsed prostate cancer serial biopsies will be performed at 4 different time points.
Sponsors
Maastricht Radiation Oncology
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Inclusion criteria
* Local relapse of prostate cancer, who is candidate for a salvage HDR treatment: * Biochemical relapse (PSA increase) * Local relapse on imaging: PSMA scan, mp-MRI * Pathology proven relapse * Willing and able to comply with the study prescriptions. * 18 years or older * Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
Exclusion criteria
* Not eligible for proposed (HDR brachytherapy) treatment: * Life expectancy \< 10 years * Distant Metastasis * Recently TURP with big urethral defect * Not able to stop anticoagulants * Flow \< 10 ml/sec • No compliance to study procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Expression of PD-(L)-1 receptor | up to 28 days | Expression of PD-(L)-1 receptor induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expression patterns of CXCL12 | up to 28 days | Expression of CXCL12 receptor induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points |
| Expression patterns of IL-23 | up to 28 days | Expression of IL-23 receptor induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points |
| Expression patterns of MDSC | up to 28 days | Expression of MDSC receptor induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points |
| Changes in HLA class I-A expression on tumor cells | up to 28 days | Changes in HLA class I-A expression on tumor cells induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points |
| Changes in HLA class I-B expression on tumor cells | up to 28 days | Changes in HLA class I-B expression on tumor cells induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points |
| Changes in HLA class I-C expression on tumor cells | up to 28 days | Changes in HLA class I-C expression on tumor cells induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points |
| Changes in T cell infiltration profiles | up to 28 days | Changes in T cell infiltration profiles induced by HDR-brachytherapy in prostate tumor biopsies of local relapses of prostate cancer of 10 patients at 4 different time points |
Countries
Netherlands
Outcome results
None listed