Cure Alveolar Soft Part Sarcoma International (iCureASPS)

“Stereotactic Ablative Radiation Therapy Induces Systemic Differences in Peripheral Blood Immunophenotype Dependent on Irradiated Site

Purpose

Despite the strong interest in combining stereotactic ablative radiation therapy (SAR) with immunotherapy, limited data characterizing the systemic immune response after SAR are available. We hypothesized that the systemic immune response to SAR would differ by irradiated site owing to inherent differences in the microenvironment of various organs.

Methods and Materials

Patients receiving SAR to any organ underwent prospective blood banking before and 1 to 2 weeks after SAR. Peripheral blood mononuclear cells (PBMCs) and serum were isolated. PBMCs were stained with fluorophore-conjugated antibodies against T and natural killer (NK) cell markers. Cells were interrogated by flow cytometry, and the results were analyzed using FlowJo software. Serum cytokine and chemokine levels were measured using Luminex. We analyzed the changes from before to after therapy using paired t tests or 1-way analysis of variance (ANOVA) with Bonferr”

https://www.sciencedirect.com/science/a ... 1618306953

Results

A total of 31 patients had evaluable PBMCs for flow cytometry and 37 had evaluable serum samples for Luminex analysis. The total number of NK cells and cytotoxic (CD56dimCD16+) NK cells decreased (P = .02) and T-cell immunoglobulin- and mucin domain–containing molecule-3–positive (TIM3+) NK cells increased (P = .04) after SAR to parenchymal sites (lung and liver) but not to bone or brain. The total memory CD4+ T cells, activated inducible co-stimulator–positive and CD25+CD4+ memory T cells, and activated CD25+CD8+ memory T cells increased after SAR to parenchymal sites but not bone or brain. The circulating levels of tumor necrosis factor-α (P = .04) and multiple chemokines, including RANTES (P = .04), decreased after SAR to parenchymal sites but not bone or brain.

Conclusions

Our data suggest SAR to parenchymal sites induces systemic immune changes, including a decrease in total and cytotoxic NK cells, an increase in TIM3+ NK cells, and an increase in activated memory CD4+ and CD8+ T cells. SAR to nonparenchymal sites did not induce these changes. By comparing the immune response after radiation to different organs, our data suggest SAR induces systemic immunologic changes that are dependent on the irradiated site.

Stereotactic Ablative Radiation Therapy Induces Systemic Differences in Peripheral Blood Immunophenotype Dependent on Irradiated Site

https://cloudfront.escholarship.org/dis ... eacn7&v=lg

Did you see what parenchymal sites they tested? and what are the parenchymal sites - lungs, liver, kidneys - i.e. organs?

Olga
Liver ,lung ,bone lescion and brain
Organs yes is my understanding .

A bone is a rigid organ that constitutes part of the vertebrate skeleton. Bones support and protect the various organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, and enable mobility.

Learn something new every day. :)

Here’s the research gate pdf


https://www.researchgate.net/publicatio ... iated_Site

Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer

Abstract
Background:
Preclinical and clinical studies suggest potential synergy between high dose per fraction focal radiation and immunotherapy. However, conventionally fractionated radiation regimens in combination with concurrent chemotherapy are more commonly administered to patients as definitive treatment and may have both immune-stimulating and -suppressive effects.

Methods:
We prospectively collected longitudinal samples from head and neck squamous cell carcinoma patients receiving definitive radiation therapy. We quantified changes in populations of circulating immune cells and chemokines CXCL9, 10, and 16. Analyses of humoral and cellular immune responses were conducted in select patients via proteomic analysis and T-cell receptor sequencing.

Results:
Treatment not only increased circulating CD-8+ T-effector cells, but also myeloid-derived suppressor cells, regulatory T cells, and checkpoint receptor-expressing T cells, particularly PD-1+ T cells. Significant decreases in CXCL10 and increases in CXLC16 were noted. Treatment also increased the percentage of unique and dominant TCR clones, and increased humoral responses as measured by proteomic array.

Conclusions:
Our results suggest that fractionated chemoradiation leads to quantifiable effects in circulating immune mediators, including a balance of stimulatory and suppressive mechanisms. These results suggest future combinations with immune checkpoint blockade.


https://www.nature.com/articles/bjc2016166

Systemic Immunotherapy for the Treatment of Brain Metastases

http://www.cureasps.org/forum/viewtopic ... 413#p11413