Cancer Communications, Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

An effective coordination of immune and non-immune cells is essential for generating optimal regional immunity to combat tumorigenesis infection at barrier tissues such as lung. Regional structures inducible bronchus-associated lymphoid tissue (iBALT) tertiary structure (TLS) play roles in modulating lung local responses. While the identification iBALTs or TLS generally dependent on conventional histology, it remains poorly understood how are spatiotemporally coordinated single-cell resolution effectively eliminate malignant invading pathogens. Recently studies have revealed presence dendritic cell (DC)-T hubs human with close association tumor immunotherapy response [1], antiviral [2], inflammation [3]. The DC-T delineates pulmonary multicellular networks level antitumor response, will profound implications diagnosis treatment cancer infection. integration technologies high-resolution spatial imaging methods has been applied reveal landscapes microenvironment (TME) relevance caner development, clinical outcome, therapy responsiveness [4]. Multicellular C-X-C motif chemokine ligand 13-positive (CXCL13+) T interferon-stimulated gene (ISG)-expressing myeloid detected luminal surface colorectal [5]. same group further existence hub [1]. This composed activated CCR7+ lysosomal-associated membrane protein 3-positive (LAMP3+) DCs (also termed mature enriched regulatory molecules, mregDCs), stem-like transcription factor 7-positive (TCF7+) programmed death 1-positive (PD-1+) CD8+ cells, C-C 19-positive (CCL19+) fibroblasts, strongly associate beneficial outcome PD-1 blockade therapy. Chemokine adhesion pathways stability organization hub, consistence report that leukocyte molecule, CD6 (ALCAM/CD166) stabilizes DC-CD8 interactions early stages against evasion [6]. intratumoral niche consisting mregDCs, CXCL13+CD4+ helper progenitor also present hepatocellular carcinoma associates [7]. combination RNA sequencing (scRNA-seq) significantly facilitated cellular molecular immunological niches transcriptional levels, multiplexed allows characterization levels. One study using imaging, quantitative analysis, machine learning mapped tumors mice human, identified interacting lymphocytes ("lymphonets") a distinctive feature anti-cancer response. Such lymphnets contain TCF1+PD-1+CD8+ progenitors gain cytotoxic populations enhance anti-tumor responses [8]. It should be noted can remodeled by TME promote malignancy metastasis [9]. recent advanced multiplex techniques discovered mregDC recruit (Tregs) form mregDC-Treg around lymphatic vessels peripheral stroma. peri-lymphatic prevents antigen trafficking draining lymph nodes (dLNs), thus inhibits promotes progression [10]. Similarly, LAMP3+ DC expressing indoleamine 2,3-dioxygenase 1 (IDO1) was shown interact exhausted CD4+ Treg cervical cancers (CC), inhibiting IDO1 could efficacy checkpoint mouse model CC [11]. Further elucidating mechanisms education reprograming versus pro-tumor novel targets screening, diagnosis, treatment. Although multiple analyzed underlying caused severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [12], few about along entire process In study, Cong et al. [2] integrated enhanced omics-sequencing (Stereo-seq) scRNA-seq specific containing three co-localized subset, Cd160+Cd8+ necrosis receptor superfamily, member 4 (Tnfrsf4)+Cd4+ 7 (Ccr7)+Ido1+ which dynamically shapes host SARS-CoV-2 (Figure 1). Chemokines, co-stimulatory factors molecules critical intercellular communication among components, emphasizing active chemotaxis adhesive after viral localizes alveoli, provides first defense microbial alveolar region, distinguished from gut-associated (GALTs) only reside deeper organs (Supplementary Table S1). rapid day first-line infection, challenging traditional idea cell-mediated adaptive requires 5∼7 days take place post addition, proliferation potent interaction between SLAM family 9 (Slamf9)+ macrophage important clearance SARS-CoV-2. virally infected Slamf9+ macrophages highly express remodeling angiogenesis genes, implying their involvement remodeling. As late 14 differentiate toward triggering expressed (Trem2)+ fructose-bisphosphatase (Fbp1)+ macrophages, accompanied downregulation inflammatory genes (Tnf), complement component 1, q subcomponent (C1q), but restoration repair collagenous (Marco) Cd36, importance compartments Moreover, distinct neutrophil subpopulations via platelet endothelial molecule (PECAM), CCL, CD80, interleukin 10 (IL-10) pathways, contributing 2). another an immune-epithelial restrain regeneration drivespost-acute sequelae corona virus disease 2019 (COVID-19) (PASC), suggesting diverse determining outcomes clinal consequences infections [13]. Immune metabolic function behavior tumor, inflammation, offer opportunities prevention related disorders. Ccr7+Ido1+ residing center phenotypically resembling mregDCs [14], evidence cues control identity fate mregDCs. Glycolysis upon CCR7 ligation supports CCR7-medited migration maintaining cytoskeleton rearrangement oligomerization, thereby supporting [15]. intermediate metabolite mevalonate pathway, farnesyl pyrophosphate (FPP), dLNs mitochondrial metabolism, consequently lead sustained germinal pathological [16]. expression tolerogenic DC2 (cDC2) producing tryptophan l-kynurenine, indispensable role metabolism controlling property cDCs [17]. Metabolic crosstalk emerges regulating DC-centered during Intra-tumoral glutamine supplementation support cDC1-mediated overcome therapeutic resistance immunotherapies [18]. melanoma-derived lactate serves trigger sterol element binding (SREBP2)-dependent activation cholesterol within TME, forming lactate-SREBP2 signaling axis driving maturation suppression immunity. DC-specific ablation inhibition SREBP2 exert effects promoting [19]. hyperglycaemia inhibit shifting composition subsets, most notably cDC1. increased glucose-to-acetyl-CoA induced alters global chromatin key DCs, metabolic-immune pathway orchestrating dysregulation [20]. intriguing identify whether glucose would affect its communications B sum, exhibit unique network CCR7-expressing cancer. These represent previously unrecognized dynamic establish surveillance homeostasis. issues biological function, regulation mechanism, remain largely unanswered worthy investigations future, examples, (1) developmental origin, functional specialization components; (2) governing initial formation, expansion, hub; (3) antigens signals determine polarization migratory DCs; (4) distribution characteristic other gastrointestinal tract, etc. Future exploration comprehensive spatiotemporal landscape understanding dictates development greatly facilitate based involved hub. integrative multi-omics analysis initiate paradigm-shifting transformation oncological provide resource scientific community understand diseases developing therapies future. Xuetao Cao Juan Liu conceived conceptualized concept this writing wrote original draft. Boyi generated figures table supervision Liu. All authors critically revised manuscript. Not applicable declare no conflicts interest. work supported Grants National Key R&D Program China (2023YFA1801400) Natural Science Foundation (92374115 82388201). applicable. Please note: publisher not responsible content functionality any information supplied authors. Any queries (other than missing content) directed corresponding author article.

Язык: Английский