1. The intraprostatic immune environment after stereotactic body radiotherapy is dominated by myeloid cells
- Author
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Michael L. Steinberg, Christopher R. King, Ekambaram Ganapathy, Matthew Rettig, Beatrice S. Knudsen, Minsong Cao, Christine Nguyen, Ramin Nazarian, Fang-I Chu, David Elashoff, Vince Basehart, Tahmineh Romero, Care Felix, Silvia Diaz-Perez, Nicholas G. Nickols, Dörthe Schaue, Nazy Zomorodian, Jae Kwak, Nathanael Kane, Lin Lin, Robert E. Reiter, Colleen Mathis, Patrick A. Kupelian, and Amar U. Kishan
- Subjects
Male ,Oncology ,Cancer Research ,Myeloid ,medicine.medical_treatment ,030232 urology & nephrology ,Prostate cancer ,0302 clinical medicine ,Prostate ,Myeloid Cells ,Cancer ,Prostatectomy ,Prostate Cancer ,Urology & Nephrology ,Middle Aged ,Neoadjuvant Therapy ,6.5 Radiotherapy and other non-invasive therapies ,Intralymphatic ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunotherapy ,Urologic Diseases ,medicine.medical_specialty ,Urology ,Clinical Trials and Supportive Activities ,Oncology and Carcinogenesis ,Radiosurgery ,Article ,Injections ,Vaccine Related ,03 medical and health sciences ,Immune system ,Clinical Research ,Internal medicine ,medicine ,Humans ,business.industry ,Evaluation of treatments and therapeutic interventions ,Injections, Intralymphatic ,Prostatic Neoplasms ,medicine.disease ,Immune checkpoint ,Radiation therapy ,Quality of Life ,Neoplasm Grading ,business - Abstract
BackgroundHundreds of ongoing clinical trials combine radiation therapy, mostly delivered as stereotactic body radiotherapy (SBRT), with immune checkpoint blockade. However, our understanding of the effect of radiotherapy on the intratumoral immune balance is inadequate, hindering the optimal design of trials that combine radiation therapy with immunotherapy. Our objective was to characterize the intratumoral immune balance of the malignant prostate after SBRT in patients.MethodsSixteen patients with high-risk, non-metastatic prostate cancer at comparable Gleason Grade disease underwent radical prostatectomy with (n = 9) or without (n = 7) neoadjuvant SBRT delivered in three fractions of 8 Gy over 5 days completed 2 weeks before surgery. Freshly resected prostate specimens were processed to obtain single-cell suspensions, and immune-phenotyped for major lymphoid and myeloid cell subsets by staining with two separate 14-antibody panels and multicolor flow cytometry analysis.ResultsMalignant prostates 2 weeks after SBRT had an immune infiltrate dominated by myeloid cells, whereas malignant prostates without preoperative treatment were more lymphoid-biased (myeloid CD45+ cells 48.4 ± 19.7% vs. 25.4 ± 7.0%; adjusted p-value = 0.11; and CD45+ lymphocytes 51.6 ± 19.7% vs. 74.5 ± 7.0%; p = 0.11; CD3+ T cells 35.2 ± 23.8% vs. 60.9 ± 9.7%; p = 0.12; mean ± SD).ConclusionSBRT drives a significant lymphoid to myeloid shift in the prostate-tumor immune infiltrate. This may be of interest when combining SBRT with immunotherapies, particularly in prostate cancer.
- Published
- 2020
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