Immune checkpoint blockade improves the activation and function of circulating mucosal-associated invariant T (MAIT) cells in patients with non-small cell lung cancer.

Mucosal-associated invariant T (MAIT) cells constitute one of the most numerous unconventional T cell subsets, and are characterized by rapid release of Th1- and Th17-associated cytokines and increased cytotoxic functions following activation. MAIT cells accumulate in tumor tissue but show an exhausted phenotype. Here, we investigated if immune checkpoint blockade (ICB) with antibodies to PD-1 or PD-L1 affects the function of circulating MAIT cells from non-small cell lung cancer patients. ICB increased the proliferation and co-expression of the activation markers HLA-DR and CD38 on MAIT cells in most patients after the first treatment cycle, irrespective of treatment outcome. Furthermore, production of cytokines, especially TNF and IL-2, also increased after treatment, as did MAIT cell polyfunctionality. These results indicate that MAIT cells respond to ICB, and that MAIT cell reinvigoration may contribute to tumor regression in patients undergoing immune checkpoint therapy.

Combinatory analysis of immune cell subsets and tumor-specific genetic variants predict clinical response to PD-1 blockade in patients with non-small cell lung cancer.

Objectives: Immunotherapy by blocking programmed death protein-1 (PD-1) or programmed death protein-ligand1 (PD-L1) with antibodies (PD-1 blockade) has revolutionized treatment options for patients with non-small cell lung cancer (NSCLC). However, the benefit of immunotherapy is limited to a subset of patients. This study aimed to investigate the value of combining immune and genetic variables analyzed within 3-4 weeks after the start of PD-1 blockade therapy to predict long-term clinical response. Materials and methodology: Blood collected from patients with NSCLC were analyzed for changes in the frequency and concentration of immune cells using a clinical flow cytometry assay. Next-generation sequencing (NGS) was performed on DNA extracted from archival tumor biopsies of the same patients. Patients were categorized as clinical responders or non-responders based on the 9 months' assessment after the start of therapy. Results: We report a significant increase in the post-treatment frequency of activated effector memory CD4+ and CD8+ T-cells compared with pre-treatment levels in the blood. Baseline frequencies of B cells but not NK cells, T cells, or regulatory T cells were associated with the clinical response to PD-1 blockade. NGS of tumor tissues identified pathogenic or likely pathogenic mutations in tumor protein P53, Kirsten rat sarcoma virus, Kelch-like ECH-associated protein 1, neurogenic locus notch homolog protein 1, and serine/threonine kinase 11, primarily in the responder group. Finally, multivariate analysis of combined immune and genetic factors but neither alone, could discriminate between responders and non-responders. Conclusion: Combined analyses of select immune cell subsets and genetic mutations could predict early clinical responses to immunotherapy in patients with NSCLC and after validation, can guide clinical precision medicine efforts.

Interfacial Engineering to Tailor the Properties of Multifunctional Ultralight Weight hBN-Polymer Composite Aerogels.

A common feature of aerogels is that they are brittle and suffer from poor mechanical properties. The development of high-performance, lightweight, and mechanically robust polymer composite aerogels may find use in a broad range of applications such as packaging, transportation, construction, electronics, and aerospace. Most aerogels are made of ceramic materials, such as silica, alumina, and carbide. These aerogels are dense and brittle. Two-dimensional (2D) layered nanostructures such as graphene, graphene oxide and hexagonal boron nitride (hBN) have promising potential in emerging technologies including those involved in extreme environmental conditions because they can withstand high temperatures, harsh chemical environments, and corrosion. Here, we report the development of highly porous, ultralightweight, and flexible aerogel composites made by the infiltration of various polymers into 2D hBN aerogels. The 2D hBN aerogels in which pore size could be controlled were fabricated using a unique self-assembly approach involving polystyrene nanoparticles as templates for ammonia borane into desired structures. We have shown that the physical, mechanical, and thermal properties of hBN-polymer composite aerogels can be tuned by the infiltration of different additives. We also performed theoretical calculations to gain insight into the interfacial interactions between the hBN-polymer structure, as the interface is critical in determining key material properties.

Crystalline Nature of Colloids in Methylammonium Lead Halide Perovskite Precursor Inks Revealed by Cryo-Electron Microscopy.

Metal halide perovskites have generated interest across many fields for the impressive optoelectronic properties achievable in films produced using facile solution-processing techniques. Previous research has revealed the colloidal nature of perovskite precursor inks and established a relationship between the colloid distribution and the film optoelectronic quality. Yet, the identity of colloids remains unknown, hindering our understanding of their role in perovskite crystallization. Here, we investigate precursor inks of the prototypical methylammonium lead triiodide perovskite using cryo-electron microscopy (cryo-EM) and show, for the first time, that the colloids are neither amorphous nor undissolved lead iodide, as previously speculated, but are a crystalline, non-perovskite material. We identify this as a perovskite precursor phase and discuss this as a potential means to understanding the role of chloride in processing. This work establishes cryo-EM as a viable technique to elucidate the nature of colloids in perovskite inks, a vital step toward a fundamental understanding of thin-film crystallization.

Effects of disorder on two-photon absorption in amorphous semiconductors.

Structural disorder inherent to amorphous materials affords them unique, tailorable properties desirable for diverse applications, but our ability to exploit these phenomena is limited by a lack of understanding of complex structure-property relationships. Here we focus on nonlinear optical absorption and derive a relationship between disorder and the two-photon absorption (2PA) coefficient. We employ an open-aperture Z-scan to measure the 2PA spectra of arsenic (III) sulfide (As2S3) chalcogenide glass films processed with two solvents that impart different levels of structural disorder. We find that the effect of solvent choice on 2PA depends on the energy of the exciting photons and explain this as a consequence of bonding disorder and electron state localization. Our results demonstrate how optical nonlinearities in As2S3 can be enhanced through informed processing and present a fundamental relationship between disorder and 2PA for a generalized amorphous solid.

Concentration dependence of As2S3 chalcogenide glass cluster size in amine solution.

Solution processing chalcogenide glasses is a common and effective first step in optoelectronic device fabrication. Arsenic(iii) sulfide (As2S3) is believed to take on a nanoscale cluster structure in n-propylamine and n-butylamine, which affects the morphology and properties of the deposited material; however, the size of these clusters and the mechanism of size determination are poorly understood. We combine experimental and analytical techniques to investigate As2S3 cluster size in n-propylamine and its dependence on solution concentration. We find that the cluster size increases with concentration and show that this trend is consistent across independent experimental techniques. We then explain these results by proposing a simplified dissolution mechanism and deriving cluster size through a free energy argument. Our findings enable informed control of chalcogenide glass cluster size during solution processing and improved property control in optoelectronic device fabrication.