Stereotactic Ablative Radiation Therapy in 3 Fractions Induces a Favorable Systemic Immune Cell Profiling in Prostate Cancer Patients

ABSTRACT

The impact of radiotherapy (RT) on immune cell status in prostate cancer (PCa) is only partially determined. The aim of this study was to assess the effect of different RT strategies on peripheral B, T, and Natural killer (NK) lymphocytes at precise longitudinal time-points in PCa. 18 patients treated with stereotactic body radiation therapy (SBRT) (40 Gy/3FRX), definitive moderate-hypofractionation (62 Gy/20FRX), or post-operative conventional-fractionation RT (66–69 Gy/30FRX) were prospectively evaluated for the immune cell profile in terms of immune cell composition, differentiation stage, cytokine production and inhibitory receptor (IR) expression. The immune-monitoring of the 18 patients revealed that RT affects the balance of systemic immune cells, with the main differences observed between SBRT and conventionally fractionated RT. SBRT favorably impacts immune response in term of increased B cells, central-memory and effector-memory CD8⁺ T cells, along with decreased Treg cells after treatment. On the contrary, conventional fractionated RT had a long-term negative effect on the systemic immune profile, including a decrease of total lymphocyte counts accompanied by an increase of neutrophils-to-lymphocytes ratio. Total B and T cells decreased and Treg-to-CD8⁺ ratio increased. Functionality of T lymphocytes were not affected by any of the 3-fractionation schedules. Interestingly, SBRT significantly up-regulates the expression of V-domain immunoglobulin suppressor of T-cell activation (VISTA) in CD8⁺ T cells in the absence of other IRs. Our results indicate the relevance of systematic immunomonitoring during RT to identify novel immune-related target to design trials of combined radio-immunotherapy as a promising strategy in the clinical management of PCa.

KEYWORDS:

• Immunomonitoring
• prostate cancer
• radiotherapy
• stereotactic body radiation therapy
• peripheral immune cells
• combined therapies
• immunotherapy

Trial registration

Clinicaltrials.gov NCT04774133, registered February 23 2021, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT04774133

Data availability statement

Research data are stored in an institutional repository and will be shared upon reasonable request to the corresponding author.

Ethics approval and consent to participate

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the ‘Regina Elena’ National Cancer Institute (protocol code RS1163/18).

Author contribution

B.P., A.F., M.B. P.N. and G.S. contributed conception and design of the study. P.N. and G.S. supervised the data. M.B., A.F. and G.S. enrolled and treated patients and collected the clinical information. B.P., I.C and P.N. designed the experiments. B.P., M.P. and S.M. performed the experiments and analyzed the data. B.P., M.B., A.F., I.C. and P.N interpreted data. I.S. and G.F performed statistical analysis. M.L.F. supplied blood samples from healthy donors. B.P., M.B. P.N. and G.S. wrote the manuscript. All authors read and agreed on the final version of the submitted manuscript.

Disclosure statement

The authors report there are no competing interests to declare

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2174721

Additional information

Funding

This work was financially supported through funding from the “Ricerca Corrente 2022” granted by the Italian Ministry of Health and partially supported by the Italian Association for Cancer Research PN AIRC IG 19822.