T cell-based immunotherapies hold promise in treating cancer by leveraging the immune system’s recognition of cancer-specific antigens1. However, their efficacy is limited in tumours with few somatic mutations and substantial intratumoural heterogeneity2,3,4. Here we introduce a previously uncharacterized class of tumour-wide public neoantigens originating from RNA splicing aberrations in diverse cancer types. We identified T cell receptor clones capable of recognizing and targeting neoantigens derived from aberrant splicing in GNAS and RPL22. In cases with multi-site biopsies, we detected the tumour-wide expression of the GNAS neojunction in glioma, mesothelioma, prostate cancer and liver cancer. These neoantigens are endogenously generated and presented by tumour cells under physiologic conditions and are sufficient to trigger cancer cell eradication by neoantigen-specific CD8+ T cells. Moreover, our study highlights a role for dysregulated splicing factor expression in specific cancer types, leading to recurrent patterns of neojunction upregulation. These findings establish a molecular basis for T cell-based immunotherapies addressing the challenges of intratumoural heterogeneity.
Ultra-hot Jupiters, an extreme class of planets not found in our solar system, provide a unique window into atmospheric processes. The extreme temperature contrasts between their day- and night-sides pose a fundamental climate puzzle: how is energy distributed? To address this, we must observe the 3D structure of these atmospheres, particularly their vertical circulation patterns, which can serve as a testbed for advanced Global Circulation Models (GCM) e.g.1. Here we show a dramatic shift in atmospheric circulation in an ultra-hot Jupiter: a unilateral flow from the hot star- facing side to the cooler space-facing side of the planet sits below an equatorial super-rotational jet stream. By resolving the vertical structure of atmospheric dynamics, we move beyond integrated global snapshots of the atmosphere, enabling more accurate identification of flow patterns and allowing for a more nuanced comparison to models. Global Circulation Models based on first principles struggle to replicate the observed circulation pattern3 underscoring a critical gap between theoretical understanding of atmospheric flows and observational evidence. This work serves as a testbed to develop more comprehensive models applicable beyond our Solar System as we prepare for the next generation of giant telescopes.
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