Purpose: Immune checkpoint inhibitors (ICI) have revolutionized cancer management. However, molecular determinants of response to ICIs remain incompletely understood. Experimental Design: We performed genomic profiling of 78 patients with non-small cell lung cancer (NSCLC) who underwent anti-PD-(L)1 therapies by both whole-exome and targeted next-generation sequencing (a 422-cancer-gene panel) to explore the predictive biomarkers of ICI response. Tumor mutation burden (TMB), and specific somatic mutations and copy-number alterations (CNA) were evaluated for their associations with immunotherapy response. Results: We confirmed that high TMB was associated with improved clinical outcomes, and TMB quantified by gene panel strongly correlated with WES results (Spearman's r ¼ 0.81). Compared with wild-type, patients with FAT1 mutations had higher durable clinical benefit (DCB, 71.4% vs. 22.7%, P ¼ 0.01) and objective response rates (ORR, 57.1% vs. 15.2%, P ¼ 0.02). On the other hand, patients with activating mutations in EGFR/ERBB2 had reduced median progression-free survival (mPFS) compared with others [51.0 vs. 70.5 days, P ¼ 0.0037, HR, 2.47; 95% confidence interval (CI), 1.32-4.62]. In addition, copy-number loss in specific chromosome 3p segments containing the tumorsuppressor ITGA9 and several chemokine receptor pathway genes, were highly predictive of poor clinical outcome (survival rates at 6 months, 0% vs. 31%, P ¼ 0.012, HR, 2.08; 95% CI, 1.09-4.00). Our findings were further validated in two independently published datasets comprising multiple cancer types. Conclusions: We identified novel genomic biomarkers that were predictive of response to anti-PD-(L)1 therapies. Our findings suggest that comprehensive profiling of TMB and the aforementioned molecular markers could result in greater predictive power of response to ICI therapies in NSCLC.
Volatile solid additives (SADs) are considered as a simple
yet
effective approach to tune the film morphology for high-performance
organic solar cells (OSCs). However, the structural effects of the
SADs on the photovoltaic performance are still elusive. Herein, two
volatilizable SADs were designed and synthesized. One is SAD1 with
twisted conformation, while the other one is planar SAD2 with the
S···O noncovalent intramolecular interactions (NIIs).
The theoretical and experimental results revealed that the planar
SAD2 with smaller space occupation can more easily insert between
the Y6 molecules, which is beneficial to form a tighter intermolecular
packing mode of Y6 after thermal treatment. As a result, the SAD2-treated
OSCs exhibited less recombination loss, more balanced charge mobility,
higher hole transfer rate, and more favorable morphology, resulting
in a record power conversion efficiency (PCE) of 18.85% (certified
PCE: 18.7%) for single-junction binary OSCs. The universality of this
study shed light on understanding the conformation effects of SADs
on photovoltaic performances of OSCs.
Psoriasis is a chronic skin inflammatory disorder, the immune mechanism of which has been profoundly elucidated in the past few years. The dominance of the interleukin (IL)-23/IL-17 axis is a significant breakthrough in the understanding of the pathogenesis of psoriasis, and treatment targeting IL-23 and IL-17 has successfully benefited patients with the disease. The skin contains a complex network of dendritic cells (DC) mainly composed of epidermal Langerhans cells, bone marrow-derived dermal conventional DC, plasmacytoid DC and inflammatory DC. As the prominent cellular source of a-interferon, tumor necrosis factor-a, IL-12 and IL-23, DC play a pivotal role in psoriasis. Thus, targeting pathogenic DC subsets is a valid strategy for alleviating and preventing psoriasis and other DC-derived diseases. In this review, we survey the known role of DC in this disease.
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