TEST:

nCounter® Immune Exhaustion Panel

This was not seen in immune cells from naïve samples, indicating that obesity leads to more chronic T cell dysfunction in metastatic lungs. Overall, even without pathogenic interference, obesity contributes to more T cell signaling and impaired CD8+ T cell activation that leads to higher T cell dysfunction once metastasis is present.

Our data shows that differentially regulated immune exhaustion targets between HCC and iCCA are of high interest in the development of clinical and therapeutic targets in liver cancer. Metabolite interconversion enzymes, such as ALDH3A1, are discussed to be essential for the activation or inactivation of anticancer drugs and could potentially affect drug treatment outcome, thereby representing potential biomarkers. Immunohistochemistry proved to be a valid diagnostic tool for ALDH3A1 expression and clinical data suggests prognostic value.

The cells were also activated in vitro both in the presence and absence of recombinant PD-L1 +/- atezolizumab and assayed for cytotoxic degranulation and production of effector cytokines...Indeed, PD-1+ Vδ1+ T cells retained effector responses to T cell receptor signalling that were inhibitable by PD-1 engagement and partially derepressed by CPI. Conclusions Our formal demonstration that Vδ1+ T cells can be suppressed by PD-1 engagement and de-repressed by anti-PD-(L)1 CPI therapy supports their utility as a predictive biomarker for therapy.

Further analysis showed upregulated expression of genes associated with senescence in immune cells from metastatic lungs of obese mice. These data suggest that obesity may increase dysfunctional states of T cells and NK cells, leading to enhanced metastatic growth of breast cancer cells.