The electroreductive coupling of chromones with benzophenones in the presence of TMSCl gave adducts reacted at the 2‐position of chromones as trimethylsilyl ethers. From 3‐methyl‐ and 3‐phenylchromones, 2,3‐cis‐adducts were formed predominantly. The cis‐adducts were isomerized to trans‐ones by treatment with DBU. The detrimethylsilylation of the adducts with 1 M HCl aq/dioxane produced the corresponding alcohols. The dehydrosiloxylation of the adducts or dehydration of the desilylated alcohols brought about 2‐diarylmethylchromones. The detrimethylsilylation of the adducts with TBAF and subsequent treatment with NaH afforded ring‐opening products. The dehydration of the ring‐opening products obtained from 3‐methyl‐ and 3‐phenylchromons brought about tetrasubstituted furans or dihydrobenzofuran‐3‐ones. The dehydrogenation of the adducts with DDQ and subsequent desilylation with 1 M HCl aq/dioxane gave 2‐(diarylhydroxymethyl)chromones.

Background We aimed to identify the relationship between thyroid transcription factor‐1 (TTF‐1) expression of lung adenocarcinoma and the efficacy of immune‐checkpoint inhibitor (ICI) therapy. Methods This retrospective multicenter study comprised patients with advanced lung adenocarcinoma treated with ICI monotherapy. We collected clinical medical records including data on TTF‐1 expression and analyzed the relationship between TTF‐1 expression and programmed death‐ligand 1 tumor proportion score (PD‐L1 TPS), objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Results In total, 108 patients with lung adenocarcinoma were analyzed. The rate of TPS ≥1% and ≥50% in patients with positive TTF‐1 expression was significantly higher than that in patients with negative TTF‐1 expression (88% vs. 60%, p < 0.001; 65% vs. 24%, p < 0.001). The ORR was significantly higher in TTF‐1 positive patients than in TTF‐1‐negative patients (38% vs. 8%, p = 0.003). Among patients with TPS ≥50% and 1%–49%, the ORR in TTF‐1 positive and negative patients was 48% (26/54) versus 17% (1/6) ( p = 0.21), and 32% (6/19) versus 11% (1/9) ( p = 0.37), respectively. The ORR for patients with TPS <1% was 0% in both the TTF‐1 negative and positive cases. The median PFS and OS was significantly longer in TTF‐1‐positive patients than in TTF‐1‐negative patients (5.4 vs. 1.6 months, p < 0.001; 18.2 vs. 8.0 months, p = 0.041). Multivariate analysis revealed that TTF‐1‐negative status was an independent unfavorable prognostic factor for PFS. Conclusion Patients with TTF‐1‐positive status receiving ICI monotherapy showed better outcomes than those with TTF‐1‐negative lung adenocarcinoma.

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Background Although vimentin is often expressed in non–small cell lung cancer (NSCLC), the association between vimentin expression and immune‐checkpoint inhibitor (ICI) efficacy remains unclear. Methods This retrospective multicenter study enrolled patients with NSCLC who received ICI treatment between December 2015 and July 2020. The authors constructed tissue microarrays and performed immunohistochemical staining with vimentin. They analyzed the relationship between vimentin expression rate and objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Results Immunohistochemically evaluable specimens on microarray blocks were available for 397 patients, of whom 343 (86%) were negative (<10%), 30 (8%) were positive (10%−49%), and 24 (6%) were highly positive (≥50%) for vimentin expression. Both rates of programmed death‐ligand 1 (PD‐L1) tumor proportion score ≥1% and ≥50% were significantly higher in the vimentin‐positive group (≥10%) than the vimentin‐negative group (<10%) (96% vs. 78%, p = .004; 64% vs. 42%, p = .006, respectively). In patients treated with ICI monotherapy, ORR, PFS, and OS were significantly better in the vimentin‐positive group (10%−49%) than in the vimentin‐negative group (<10%) (54% vs. 25%, p = .003, median = 7.9 vs. 3.2 months, p = .011; median = 27.0 vs. 13.6 months, p = .015, respectively), whereas there was no significant difference in PFS and OS between the vimentin highly positive group (≥50%) and the vimentin‐negative group (<10%) (median = 3.4 vs. 3.2 months, p = .57; median = 7.2 vs. 13.6 months, p = .086, respectively). Conclusions Vimentin expression correlated with PD‐L1 expression and ICI efficacy. Plain Language Summary We constructed tissue microarrays and performed immunohistochemical staining with vimentin on 397 patients with advanced non–small cell lung cancer who were treated with immune‐checkpoint inhibitor (ICI). The vimentin‐positive group who were treated with ICI monotherapy showed significantly better objective response rate, progression‐free survival, and overall survival than the vimentin negative group. The measurement of vimentin expression will aid in determining appropriate immunotherapy strategies.

It is unclear whether tumor vascular endothelial growth factor receptor 2 expression affects the therapeutic efficacy of immune‐checkpoint inhibitors and antiangiogenic agents. This retrospective, multicenter study included patients with advanced non–small cell lung cancer who were treated with immune‐checkpoint inhibitors. We constructed tissue microarrays and performed immunohistochemistry with an anti‐vascular endothelial growth factor receptor 2 antibody. We analyzed immune and tumor cell staining separately in order to determine their correlation with the objective response rate, progression‐free survival, and overall survival in patients receiving immune‐checkpoint inhibitors. Of 364 patients, 37 (10%) expressed vascular endothelial growth factor receptor 2 in immune cells and 165 (45%) in tumor cells. The objective response rate, progression‐free survival, and overall survival were significantly worse in patients treated with immune checkpoint inhibitor monotherapy who expressed vascular endothelial growth factor receptor 2 in immune cells than those who did not (10% vs 30%, p = 0.028; median = 2.2 vs 3.6 months, p = 0.012; median = 7.9 vs 17.0 months, p = 0.049, respectively), while there was no significant difference based on tumor cell expression (24% vs 30%, p = 0.33; median = 3.1 vs 3.5 months, p = 0.55; median = 13.6 vs 16.8 months, p = 0.31). There was no significant difference in overall survival between patients treated with and without antiangiogenic agents in any treatment period based on vascular endothelial growth factor receptor 2 expression. Immune checkpoint inhibitor efficacy was limited in patients expressing vascular endothelial growth factor receptor 2 in immune cells.