Highlights d Lung cancer progression is accompanied by a stereotypic expansion of heterogeneity d Cell state heterogeneity arises largely independently of genetic variation d State transitions occur via an HPCS harboring high differentiation and growth capacity d The HPCS is drug resistant and portends poor patient survival across all cancers

Highlights d Longitudinal scRNA-seq of tumor-specific TCF-1 + CD8 + T cells in KP lung adenocarcinoma d Identified a proliferative Slamf6 + TCF-1 + T cell subset and a non-cycling SlamF6 À subset d The lymph node contains a recruitable reservoir of functional TCF-1 + CD8 + T cells d Flt3L+CD40 boosts cDC1, increases TCF-1 + CD8 + T cell frequencies, decreases tumor burden

Eliciting broadly neutralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into new territories is an important goal of vaccine design. To define bNAb targets, we characterized 28 antibodies belonging to expanded and hypermutated clonal families identified by transcriptomic analysis of single plasmablasts from DENV-infected individuals. Among these, we identified J9 and J8, two somatically related bNAbs that potently neutralized DENV1-4. Mutagenesis studies showed that the major recognition determinants of these bNAbs are in E protein domain I, distinct from the only known class of human bNAbs against DENV with a well-defined epitope. B cell repertoire analysis from acute-phase peripheral blood suggested that J9 and J8 followed divergent somatic hypermutation pathways, and that a limited number of mutations was sufficient for neutralizing activity. Our study suggests multiple B cell evolutionary pathways leading to DENV bNAbs targeting a new epitope that can be exploited for vaccine design.

Introduction The present study aims to evaluate the short-term and long-term outcomes of patients undergoing restorative proctocolectomy (RPC) for Crohn's disease (CD) and Indeterminate colitis (IC) and to identify factors associated with adverse outcomes.