Highlights d Pan-cancer analysis reveals heterogeneity in tumorinfiltrating myeloid cell composition d The ratio of TNF + versus VEGFA + mast cells underlines their cancer-type-specific functions d LAMP3 + cDCs are widely present, with diverse developmental origins and functions d Pro-angiogenic TAMs exhibit distinct expression profiles across different cancer types

Highlights d Transposon screen in Salmonella identifies SopF, a xenophagy-specific inhibitor d CRISPR screen identifies the V-ATPase-ATG16L1 axis that initiates xenophagy d SopF disrupts infection-induced V-ATPase-ATG16L1 association to promote replication d SopF ADP-ribosylates Gln124 of ATP6V0C in the V-ATPase to block bacterial autophagy

Mouse caspase-11 and human caspase-4 and caspase-5 recognize cytosolic lipopolysaccharide (LPS) to induce pyroptosis by cleaving the pore-forming protein GSDMD [1][2][3][4][5] . This non-canonical inflammasome defends against Gram-negative bacteria 6,7 . Shigella flexneri, which causes bacillary dysentery, lives freely within the host cytosol where these caspases reside. However, the role of caspase-11mediated pyroptosis in S. flexneri infection is unknown. Here we show that caspase-11 did not protect mice from S. flexneri infection, in contrast to infection with another cytosolic bacterium, Burkholderia thailandensis 8 . S. flexneri evaded pyroptosis mediated by caspase-11 or caspase 4 (hereafter referred to as caspase-11/4) using a type III secretion system (T3SS) effector, OspC3. OspC3, but not its paralogues OspC1 and 2, covalently modified caspase-11/4; although it used the NAD + donor, this modification was not ADP-ribosylation. Biochemical dissections uncovered an ADPriboxanation modification on Arg314 and Arg310 in caspase-4 and caspase-11, respectively. The enzymatic activity was shared by OspC1 and 2, whose ankyrin-repeat domains, unlike that of OspC3, could not recognize caspase-11/4. ADP-riboxanation of the arginine blocked autoprocessing of caspase-4/11 as well as their recognition and cleavage of GSDMD. ADP-riboxanation of caspase-11 paralysed pyroptosis-mediated defence in Shigella-infected mice and mutation of ospC3 stimulated caspase-11and GSDMD-dependent anti-Shigella humoral immunity, generating a vaccine-like protective effect. Our study establishes ADP-riboxanation of arginine as a bacterial virulence mechanism that prevents LPS-induced pyroptosis.Intracellular S. flexneri infection causes shigellosis in humans. Although most intracellular bacteria reside in vacuoles, S. flexneri, like Burkholderia spp., live freely in the host cytosol, inevitably exposing their LPS to caspase-11/4. Wild-type (WT) mice, unlike Casp11 −/− mice, survived B. thailandensis infection 8 (Fig. 1a, Extended Data Fig. 1a). Mice are increasingly being used as a surrogate host for S. flexneri. Unexpectedly, both WT and Casp11 −/− mice succumbed to lethal S. flexneri infection (Fig. 1a) and tolerated similarly the low-dose challenge (Extended Data Fig. 1a). Given the absence of caspase-11-mediated protection, we assayed non-canonical inflammasome activation upon S. flexneri infection. Casp1 −/− immortalized bone marrow-derived macrophages (iBMDMs) were used to avoid interference by the canonical inflammasome. Although B. thailandensis and S. Typhimurium ΔsifA induced Casp11-dependent GSDMD cleavage and pyroptosis 8 , S. flexneri triggered little pyroptosis (Fig. 1b) despite a higher infection efficiency (Extended Data Fig. 1b). In epithelium-derived human SiHa and A431 cells, S. flexneri, unlike S. Typhimurium ΔsifA, also did not activate the caspase-4-GSDMD pyroptosis pathway (Fig. 1b, Extended Data Fig. 1c, d). Purified LPS from S. flexneri was highly pro-pyroptotic (Extended Data Fig. 1e). Thus, S. flexneri evaded cas...

Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or race as well as 369 novel ones associated with patient survival, clinical stage, tumor metastasis or recurrence. Integrated in a user-friendly online portal, the expanded catalog of human lncRNAs provides a valuable resource for investigating lncRNA function in both human biology and cancer development.