Purpose: The study aimed to evaluate the immune response in untreated distant tumors following
Y90-radioembolization for colorectal liver metastases (CRLM).
Material and Methods: Ten patients (nine male) with microsatellite-stable (MSS) CRLM with over five lesions
were included. A baseline biopsy was performed before the Y90-radioembolization treatment
of one liver lobe, followed by a second biopsy of yet untreated tumors in the other
lobe directly before the second treatment (median interval between biopsies 13(4-49)
days. Tumor biopsies and peripheral blood mononuclear cells (PBMCs) were analyzed
for immune activity, including PD1, CD4, CD8, FoxP3, and CD68 in the tumor samples
by multiplex immunophenotyping, while PBMCs were analyzed for quantification of lymphoid
cell populations and expression of checkpoint molecules, including PD-1, TIGIT, CTLA-4,
and TIM-3. Patients with an objective response or stable disease six months post-therapy
were classified as “responders.”
Results: At baseline, biopsies of responders displayed lower FoxP3+cell and co-location of
CD4+FoxP3+cell density compared to nonresponders (both p=0.02). At the second biopsy,
nonresponders demonstrated higher CD68+macrophage density (p=0.0014). Responders exhibited
fewer CD4+FoxP3+regulatory T cells than CD8+T cells at both time points (p=0.02 and
p=0.0428). At the second biopsy, nonresponders tended to have an increased CD8+PD1+/CD8+ratio
(p=0.062). Flow cytometry of nonresponders showed lower CD8+PD1+T cell density and
CD8+PD1+/CD8+ratio at both timepoints.
Conclusion: Y90-radioembolization induces local immunogenic effects in untreated MSS CRLM lesions
and systemic exhaustion of immune cells in nonresponders. The role of synergism of
Y90-radioembolization and checkpoint inhibition warrants further investigation.
