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The intraprostatic immune environment after stereotactic body radiotherapy is dominated by myeloid cells

Prostate Cancer and Prostatic Diseases volume 24, pages 135–139 (2021)Cite this article

Subjects

Abstract

Background:

Hundreds 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.

Methods:

Sixteen 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.

Results:

Malignant 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).

Conclusion:

SBRT 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.

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Fig. 1: Prostate SBRT drives a lymphoid-to-myeloid shift in the balance of infiltrating immune cells.
Fig. 2: Irradiated prostate cancer patients cluster into treatment cohorts according to immune cell infiltrates.

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Acknowledgements

We acknowledge NIH grants: 5R01CA191234-05 (DS), UCLA Prostate SPORE P50CA0912131 (RR, NN), Prostate Cancer Foundation Young Investigator Award (NN, AK). We would like to express our sincere thanks to all the patients and to the clinical research staff.

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Authors and Affiliations

  1. Radiation Oncology at UCLA, Los Angeles, CA, USA

    Nicholas G. Nickols, Ekambaram Ganapathy, Christine Nguyen, Nathanael Kane, Silvia Diaz-Perez, Care Felix, Vince Basehart, Amar U. Kishan, Christopher R. King, Patrick A. Kupelian, Michael L. Steinberg, Minsong Cao, Fang-I Chu & Dörthe Schaue

  2. Urology at UCLA, Los Angeles, CA, USA

    Nicholas G. Nickols, Lin Lin, Ramin Nazarian, Colleen Mathis, Nazy Zomorodian, Jae Kwak, Amar U. Kishan, Matthew B. Rettig & Robert E. Reiter

  3. VA Greater Los Angeles Healthcare System, Radiation Therapy Service, Los Angeles, CA, USA

    Nicholas G. Nickols

  4. UCLA Jonsson Compressive Cancer Center, Los Angeles, CA, USA

    Nicholas G. Nickols, Amar U. Kishan, Matthew B. Rettig, Michael L. Steinberg, David Elashoff, Robert E. Reiter & Dörthe Schaue

  5. Pathology and Laboratory Medicine and Biomedical Sciences at Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Beatrice S. Knudsen

  6. Division of General Internal Medicine and Health Services Research at UCLA, Los Angeles, CA, USA

    Tahmineh Romero & David Elashoff

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Correspondence to Dörthe Schaue.

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Nickols, N.G., Ganapathy, E., Nguyen, C. et al. The intraprostatic immune environment after stereotactic body radiotherapy is dominated by myeloid cells. Prostate Cancer Prostatic Dis 24, 135–139 (2021). https://doi.org/10.1038/s41391-020-0249-8

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