Immunotherapy has shown clinical benefit in patients with non-small-cell lung cancer (NSCLC). Due to the limited response of monotherapy, combining immune checkpoint inhibitors (ICIs) and chemotherapy is considered a treatment option for advanced NSCLC. However, the mechanism of combined therapy and the potential patient population that could benefit from combined therapy remain undetermined. Here, we developed an NSCLC model based on the published quantitative systems pharmacology (QSP)-immuno-oncology platform by making necessary adjustments. After calibration and validation, the established QSP model could adequately characterise the biological mechanisms of action of the triple combination of atezolizumab, nab-paclitaxel, and carboplatin in patients with NSCLC, and identify predictive biomarkers for precision dosing. The established model could efficiently characterise the objective response rate and duration of response of the IMpower131 trial, reproducing the efficacy of alternative dosing. Furthermore, CD8+ and CD4+ T cell densities in tumours were found to be significantly related to the response status. This significant extension of the QSP model not only broadens its applicability but also more accurately reflects real-world clinical settings. Importantly, it positions the model as a critical foundation for model-informed drug development and the customisation of treatment plans, especially in the context of combining single-agent ICIs with platinum-doublet chemotherapy.
We study the properties of a weakly interacting Bose-Einstein condensate (BEC) in a flat band lattice system by using the multiband Bogoliubov theory and discover fundamental connections to the underlying quantum geometry. In a flat band, the speed of sound and the quantum depletion of the condensate are dictated by the quantum geometry, and a finite quantum distance between the condensed and other states guarantees stability of the BEC. Our results reveal that a suitable quantum geometry allows one to reach the strong quantum correlation regime even with weak interactions.
The ground state and transport properties of the Lieb lattice flat band in the presence of an attractive Hubbard interaction are considered. It is shown that the superfluid weight can be large even for an isolated and strictly flat band. Moreover the superfluid weight is proportional to the interaction strength and to the quantum metric, a band structure quantity derived solely from the flat-band Bloch functions. These predictions are amenable to verification with ultracold gases and may explain the anomalous behavior of the superfluid weight of high-T_{c} superconductors.
