Toward Transformable Photonics: Reversible Deforming Soft Cavities, Controlling Their Resonance Split and Directional Emission

We report on reversible and continuously deformable soft micro-resonators and the control of their resonance split and directional emission. Assisted by computerized holographic-tweezers, functioning as an optical deformer of our device, we gradually deform the shape and change the functionality of a droplet whispering-gallery cavity. For example, we continuously deform hexagonal cavities to rectangular ones and demonstrate switching to directionally emitting mode-of-operation, or splitting a resonant mode to a 10-GHz separated doublet. A continuous trend of improving spatial light modulators and tweezers suggests that our method is scalable and can control the shape and functionality of many individual devices. We also demonstrate optional solidification, proving the feasibility of transformer-enabled applications, including in printing optical circuits and multiwavelength optical networks

3301763.pdf

Supplemental document latex zi

Combined presentation and immunogenicity analysis reveals a recurrent RAS.Q61K neoantigen in melanoma

Neoantigens are now recognized drivers of the antitumor immune response. Recurrent neoantigens, shared among groups of patients, have thus become increasingly coveted therapeutic targets. Here, we report on the data-driven identification of a robustly presented, immunogenic neoantigen that is derived from the combination of HLA-A*01:01 and RAS.Q61K. Analysis of large patient cohorts indicated that this combination applies to 3% of patients with melanoma. Using HLA peptidomics, we were able to demonstrate robust endogenous presentation of the neoantigen in 10 tumor samples. We detected specific reactivity to the mutated peptide within tumor-infiltrating lymphocytes (TILs) from 2 unrelated patients, thus confirming its natural immunogenicity. We further investigated the neoantigen-specific clones and their T cell receptors (TCRs) via a combination of TCR sequencing, TCR overexpression, functional assays, and single-cell transcriptomics. Our analysis revealed a diverse repertoire of neoantigen-specific clones with both intra- and interpatient TCR similarities. Moreover, 1 dominant clone proved to cross-react with the highly prevalent RAS.Q61R variant. Transcriptome analysis revealed a high association of TCR clones with specific T cell phenotypes in response to cognate melanoma, with neoantigen-specific cells showing an activated and dysfunctional phenotype. Identification of recurrent neoantigens and their reactive TCRs can promote "off-theshelf" precision immunotherapies, alleviating limitations of personalized treatments