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Adoptive transfer of antigen-specific T cells represents a major advance in cancer immunotherapy, with robust clinical outcomes in some patients.sup.1. Both the number of transferred T cells and their differentiation state are critical determinants of effective responses.sup.2,3. T cells can be expanded with T cell receptor (TCR)-mediated stimulation and interleukin-2, but this can lead to differentiation into effector T cells.sup.4,5 and lower therapeutic efficacy.sup.6, whereas maintenance of a more stem-cell-like state before adoptive transfer is beneficial.sup.7. Here we show that H9T, an engineered interleukin-2 partial agonist, promotes the expansion of CD8.sup.+ T cells without driving terminal differentiation. H9T led to altered STAT5 signalling and mediated distinctive downstream transcriptional, epigenetic and metabolic programs. In addition, H9T treatment sustained the expression of T cell transcription factor 1 (TCF-1) and promoted mitochondrial fitness, thereby facilitating the maintenance of a stem-cell-like state. Moreover, TCR-transgenic and chimeric antigen receptor-modified CD8.sup.+ T cells that were expanded with H9T showed robust anti-tumour activity in vivo in mouse models of melanoma and acute lymphoblastic leukaemia. Thus, engineering cytokine variants with distinctive properties is a promising strategy for creating new molecules with translational potential. H9T, an engineered IL-2 partial agonist, promotes the expansion of T cells while maintaining a stem-cell-like state, leading to improved efficacy of adoptive cell therapy in mouse models of melanoma and acute lymphoblastic leukaemia., Author(s): Fei Mo [sup.1] , Zhiya Yu [sup.2] , Peng Li [sup.1] , Jangsuk Oh [sup.1] , Rosanne Spolski [sup.1] , Liang Zhao [sup.3] , Caleb R. Glassman [sup.4] , [...]

Compressing the optical field to the atomic scale opens up possibilities for directly observing individual molecules, offering innovative imaging and research tools for both physical and life sciences. However, the diffraction limit imposes a fundamental constraint on how much the optical field can be compressed, based on the achievable photon momentum1,2. In contrast to dielectric structures, plasmonics offer superior field confinement by coupling the light field with the oscillations of free electrons in metals3–6. Nevertheless, plasmonics suffer from inherent ohmic loss, leading to heat generation, increased power consumption and limitations on the coherence time of plasmonic devices7,8. Here we propose and demonstrate singular dielectric nanolasers showing a mode volume that breaks the optical diffraction limit. Derived from Maxwell’s equations, we discover that the electric-field singularity sustained in a dielectric bowtie nanoantenna originates from divergence of momentum. The singular dielectric nanolaser is constructed by integrating a dielectric bowtie nanoantenna into the centre of a twisted lattice nanocavity. The synergistic integration surpasses the diffraction limit, enabling the singular dielectric nanolaser to achieve an ultrasmall mode volume of about 0.0005 λ3 (λ, free-space wavelength), along with an exceptionally small feature size at the 1-nanometre scale. To fabricate the required dielectric bowtie nanoantenna with a single-nanometre gap, we develop a two-step process involving etching and atomic deposition. Our research showcases the ability to achieve atomic-scale field localization in laser devices, paving the way for ultra-precise measurements, super-resolution imaging, ultra-efficient computing and communication, and the exploration of light–matter interactions within the realm of extreme optical field localization.Singularity enables breaking the optical diffraction limit in a dielectric nanolaser. [ABSTRACT FROM AUTHOR]

Laser science has been successful in producing increasingly high-powered, faster and smaller coherent light sources (1-9). Examples of recent advances are microscopic lasers that can reach the diffraction limit, based on photonic crystals (3) , metal-clad cavities (4) and nanowiress (5-7). However, such lasers are restricted, both in optical mode size and physical device dimension, to being larger than half the wavelength of the optical field, and it remains a key fundamental challenge to realize ultracompact lasers that can directly generate coherent optical fields at the nanometre scale, far beyond the diffraction limit (10,11) . A way of addressing this issue is to make use of surface plasmons (12,13) which are capable of tightly localizing light, but so far ohmic losses at optical frequencies have inhibited the realization of truly nanometre-scale lasers based on such approaches (14,15). A recent theoretical work predicted that such losses could be significantly reduced while maintaining ultrasmall modes in a hybrid plasmonic waveguide (16). Here we report the experimental demonstration of nanometre-scale plasmonic lasers, generating optical modes a hundred times smaller than the diffraction limit. We realize such lasers using a hybrid plasmonic waveguide consisting of a high-gain cadmium sulphide semiconductor nanowire, separated from a silver surface by a 5-nm-thick insulating gap. Direct measurements of the emission lifetime reveal a broad-band enhancement of the nanowire's exciton spontaneouse-mission rate by up to six times owing to the strong mode confinement (17) and the signature of apparently threshold-less lasing. Because plasmonic modes have no cutoff, we are able to demonstrate downscaling of the lateral dimensions of both the device and the optical mode. Plasmonic lasers thus offer the possibility of exploring extreme interactions between light and matter, opening up new avenues in the fields of active photonic circuits (18), bio-sensing (19) and quantum information technology (20)., Surface plasmon polaritons are the key to breaking down the diffraction limit of conventional optics because they allow the compact storage of optical energy in electron oscillations at the interfaces [...]

Adoptive transfer of antigen-specific T cells represents a major advance in cancer immunotherapy, with robust clinical outcomes in some patients1. Both the number of transferred T cells and their differentiation state are critical determinants of effective responses2,3. T cells can be expanded with T cell receptor (TCR)-mediated stimulation and interleukin-2, but this can lead to differentiation into effector T cells4,5 and lower therapeutic efficacy6, whereas maintenance of a more stem-cell-like state before adoptive transfer is beneficial7. Here we show that H9T, an engineered interleukin-2 partial agonist, promotes the expansion of CD8+ T cells without driving terminal differentiation. H9T led to altered STAT5 signalling and mediated distinctive downstream transcriptional, epigenetic and metabolic programs. In addition, H9T treatment sustained the expression of T cell transcription factor 1 (TCF-1) and promoted mitochondrial fitness, thereby facilitating the maintenance of a stem-cell-like state. Moreover, TCR-transgenic and chimeric antigen receptor-modified CD8+ T cells that were expanded with H9T showed robust anti-tumour activity in vivo in mouse models of melanoma and acute lymphoblastic leukaemia. Thus, engineering cytokine variants with distinctive properties is a promising strategy for creating new molecules with translational potential.H9T, an engineered IL-2 partial agonist, promotes the expansion of T cells while maintaining a stem-cell-like state, leading to improved efficacy of adoptive cell therapy in mouse models of melanoma and acute lymphoblastic leukaemia. [ABSTRACT FROM AUTHOR]