Synthesis and styrene copolymerization of novel fluoro, methoxy and methyl ring-disubstituted octyl phenylcyanoacrylates

Novel fluoro, methoxy, and methyl ring-disubstituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 2-fluoro-3-methoxy, 2-fluoro-4-methoxy, 2-fluoro-5-methoxy, 2-fluoro-6-methoxy, 3-fluoro-4-methoxy, 4-fluoro-3-methoxy, 2-fluoro-5-methyl, 2-fluoro-6-methyl, 3-fluoro-4-methyl, 4-fluoro-2-methyl, 4-fluoro-3-methyl) were prepared and copolymerized with styrene. The acrylates were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-disubstituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the acrylates were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis

Baseline immunosuppressive spatiotypes in adolescent and young adult melanoma patients treated with checkpoint immunotherapy

We compared the transcriptomic, genomic, and spatial cellular profiles of the tumor microenvironment (TME) in AYA and adult melanomas to determine the pathways associated with ICI outcomes in AYA patients. We identified two ICI-resistant spatiotypes of AYA melanoma with distinct stroma infiltrating lymphocytes (SILs) unique from adult TME; SILhigh subtype was enriched for regulatory T-cells in the peritumoral space and showed alternative checkpoint expression (e.g. TIM3, ICOS), while the SILlow subtype showed a lack of immune induction. We further established a novel YIM (young immunosuppressive melanoma) score for predicting ICI response for AYA patients and proposed personalized therapeutic strategies for the ICI-resistant subgroups