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This study investigated the influence of surface wettability on competitive protein adsorption and the initial attachment of osteoblasts. A thin-film coating of hexamethyldisiloxane (HMDSO) and subsequent O(2)-plasma treatment was carried out on substrates with a mirror surface in order to create a wide range of wettabilities. The adsorption behavior of fibronectin (Fn) and albumin (Alb) in both individual and competitive mode, and the initial attachment of mouse osteoblastic cells (MC3T3-E1) over a wide range of wettabilities were investigated. The contact angle of HMDSO coatings without O(2)-plasma treatment against double-distilled water was more than 100 degrees, whereas it dramatically decreased after the O(2)-plasma treatment to almost 0 degrees, resulting in super-hydrophilicity. Individually, Fn adsorption showed a biphasic inclination, whereas Alb showed greater adsorption to hydrophobic surfaces. In the competitive mode, in a solution containing both Fn and Alb, Fn showed greater adsorption on hydrophilic surfaces, whereas Alb predominantly adsorbed on hydrophobic surfaces. The initial attachment of osteoblastic cells increased with an increase in surface wettability, in particular, on a super-hydrophilic surface, which correlated well with Fn adsorption in the competitive mode. These results suggest that Fn adsorption may be responsible for increasing cell adhesion on hydrophilic surfaces in a body fluid or culture media under physiological conditions.

Anti-PD-1 treatment has shown unprecedented clinical success in the treatment of non-small-cell lung cancer (NSCLC), but the underlying mechanisms remain incompletely understood. Here, we performed temporal single-cell RNA and paired T-cell receptor sequencing on 47 tumor biopsies from 36 patients with NSCLC following PD-1-based therapies. We observed increased levels of precursor exhausted T (Texp) cells in responsive tumors after treatment, characterized by low expression of coinhibitory molecules and high expression of GZMK. By contrast, nonresponsive tumors failed to accumulate Texp cells. Our data suggested that Texp cells were unlikely to be derived from the reinvigoration of terminally exhausted cells; instead, they were accumulated by (1) local expansion and (2) replenishment by peripheral T cells with both new and pre-existing clonotypes, a phenomenon we named clonal revival. Our study provides insights into mechanisms underlying PD-1-based therapies, implicating clonal revival and expansion of Texp cells as steps to improve NSCLC treatment.

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