Immunomonitoring in prostate cancer patients treated with 3 different radiotherapy strategies
OC-0426
Abstract
Immunomonitoring in prostate cancer patients treated with 3 different radiotherapy strategies
Authors: Marta Bottero1, Adriana Faiella1, Belinda Palermo2, Isabella Sperduti3, Serena Masi4, Maria Laura Foddai5, Iole Cordone4, Paola Nisticò2, Giuseppe Sanguineti1
1IRCCS Regina Elena National Cancer Institute, Radiation Oncology, Rome, Italy; 2IRCCS Regina Elena National Cancer Institute, Unit Tumor Immunology and Immunotherapy, Rome, Italy; 3IRCCS Regina Elena National Cancer Institute, Biostatistical Unit, Rome, Italy; 4IRCCS Regina Elena National Cancer Institute, Clinical Pathology and Cancer Biobank, Rome, Italy; 5IRCCS Regina Elena National Cancer Institute, Transfusion Medicine, Rome, Italy
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Purpose or Objective
To assess the effect of different radiotherapy (RT) strategies on peripheral B, T, and Natural killer lymphocytes at precise longitudinal time points in prostate cancer (PCa).
Material and Methods
Blood collection were prospectively collected from 18 PCa patients at baseline, 3 hours after the first dose of RT, midpoint, RT completion, 6 and 12 months after treatment-end. Accrued patients were treated as it follows: stereotactic body radiation therapy (SBRT) (prostate only, 40 Gy/3FRX, N=5), definitive moderate-hypofractionation (prostate + seminal vesicle,62 Gy/20FRX, N=6), post-operative conventional-fractionation RT (prostate bed + pelvic lymph-nodes, 66-69 Gy/30FRX, N=7). A complete blood count and an in-depth immune cells profile were performed. Fresh blood and isolated peripheral blood mononuclear cells were evaluated by multicolor flow cytometry in terms of immune cell composition, differentiation stage, cytokine production and inhibitory receptor (IR) expression.
Results
The immunomonitoring of 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 (CD19+), central-memory (CCR7+CD45RA-) and effector-memory (CCR7-CD45RA-) CD8+ T cells, along with decreased Treg cells (CD3+CD4+CD25highCD127-) 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.
Conclusion
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.