Leucine-tRNA-synthase-2-expressing B cells contribute to colorectal cancer immunoevasion.

Immunoregulatory B cells impede antitumor immunity through unknown features and mechanisms. We report the existence of leucine-tRNA-synthase-2 (LARS2)-expressing B cell (LARS B) subset with a transforming growth factor-ß1 (TGF-ß1)-dominant regulatory feature in both mouse and human progressive colorectal cancer (CRC). Of note, LARS B cells exhibited a leucine nutrient preference and displayed active mitochondrial aminoacyl-tRNA biosynthesis. They were located outside the tertiary lymphoid structure and correlated with colorectal hyperplasia and shortened survival in CRC patients. A leucine diet induced LARS B cell generation, whereas LARS B cell deletion by Lars2 gene ablation or leucine blockage repressed CRC immunoevasion. Mechanistically, LARS2 programmed mitochondrial nicotinamide adenine dinucleotide (NAD+) regeneration and oxidative metabolism, thus determining the regulatory feature of LARS B cells in which the NAD-dependent protein deacetylase sirtuin-1 (SIRT1) was involved. We propose a leucine-dieting scheme to inhibit LARS B cells, which is safe and useful for CRC therapy.

Fluctuation of lysosomal protein degradation in neural stem cells of the postnatal mouse brain.

Lysosomes are intracellular organelles responsible for degrading diverse macromolecules delivered from several pathways, including the endo-lysosomal and autophagic pathways. Recent reports have suggested that lysosomes are essential for regulating neural stem cells in developing, adult and aged brains. However, the activity of these lysosomes has yet to be monitored in these brain tissues. Here, we report the development of a new probe to measure lysosomal protein degradation in brain tissue by immunostaining. Our results indicate that lysosomal protein degradation fluctuates in neural stem cells of the hippocampal dentate gyrus, depending on age and brain disorders. Neural stem cells increase their lysosomal activity during hippocampal development in the dentate gyrus, but aging and aging-related disease reduce lysosomal activity. In addition, physical exercise increases lysosomal activity in neural stem cells and astrocytes in the dentate gyrus. We therefore propose that three different stages of lysosomal activity exist: the state of increase during development, the stable state during adulthood and the state of reduction due to damage caused by either age or disease.

Oncogenic and immunological roles of RACGAP1 in pan-cancer and its potential value in nasopharyngeal carcinoma.

A particular GTPase-activating protein called RACGAP1 is involved in apoptosis, proliferation, invasion, metastasis, and drug resistance in a variety of malignancies. Nevertheless, the role of RACGAP1 in pan-cancer was less studied, and its value of the expression and prognostic of nasopharyngeal carcinoma (NPC) has not been explored. Hence, the goal of this study was to investigate the oncogenic and immunological roles of RACGAP1 in various cancers and its potential value in NPC. We comprehensively analyzed RACGAP1 expression, prognostic value, function, methylation levels, relationship with immune cells, immune infiltration, and immunotherapy response in pan-cancer utilizing multiple databases. The results discovered that RACGAP1 expression was elevated in most cancers and suggested poor prognosis, which could be related to the involvement of RACGAP1 in various cancer-related pathways such as the cell cycle and correlated with RACGAP1 methylation levels, immune cell infiltration and reaction to immunotherapy, and chemoresistance. RACGAP1 could inhibit anti-tumor immunity and immunotherapy responses by fostering immune cell infiltration and cytotoxic T lymphocyte dysfunction. Significantly, we validated that RACGAP1 mRNA and protein were highly expressed in NPC. The Gene Expression Omnibus database revealed that elevated RACGAP1 expression was associated with shorter PFS in patients with NPC, and RACGAP1 potentially influenced cell cycle progression, DNA replication, metabolism, and immune-related pathways, resulting in the recurrence and metastasis of NPC. This study indicated that RACGAP1 could be a potential biomarker in pan-cancer and NPC.

Achieving Long-Lived Charge Separated State through Ultrafast Interfacial Hole Transfer in Redox Sites-Isolated CdS Nanorods for Enhanced Photocatalysis.

As opposed to natural photosynthesis, a significant challenge in a semiconductor-based photocatalyst is the limited hole extraction efficiency, which adversely affects solar-to-fuel efficiency. Recent studies have demonstrated that photocatalysts featuring spatially isolated dual catalytic oxidation/reduction sites can yield enhanced hole extraction efficiencies. However, the decay dynamics of excited states in such photocatalysts have not been explored. Here a ternary barbell-shaped CdS/MoS2/Cu2S heterostructure is prepared, comprising CdS nanorods (NRs) interfaced with MoS2 nanosheets at both ends and Cu2S nanoparticles on the sidewall. By using transient absorption (TA) spectra, highly efficient charge separation within the CdS/MoS2/Cu2S heterostructure are identified. This is achieved through directed electron transfer to the MoS2 tips at a rate constant of >8.3 × 109 s-1 and rapid hole transfer to the Cu2S nanoparticles on the sidewall at a rate of >6.1 × 1010 s-1, leading to an exceptional overall charge transfer constant of 2.3 × 1011 s-1 in CdS/MoS2/Cu2S. The enhanced hole transfer efficiency results in a remarkably prolonged charge-separated state, facilitating efficient electron accumulation within the MoS2 tips. Consequently, the ternary CdS/MoS2/Cu2S heterostructure demonstrates a 22-fold enhancement in visible-light-driven H2 generation compare to pure CdS nanorods. This work highlights the significance of efficient hole extraction in enhancing the solar-to-H2 performance of semiconductor-based heterostructure.

Ten-eleven translocation-2 inactivation restrains IL-10-producing regulatory B cells to enable antitumor immunity in hepatocellular carcinoma.

BACKGROUND AND AIMS: IL-10-producing regulatory B cells (IL-10 + B cells), a dominant regulatory B cell (Breg) subset, foster tumor progression. However, the mechanisms underlying their generation in HCC are poorly understood. Ten-eleven translocation-2 (TET2), a predominant epigenetic regulatory enzyme in B cells, regulates gene expression by catalyzing demethylation of 5-methylcytosine into 5-hydroxymethyl cytosine (5hmC). In this study, we investigated the role of TET2 in IL-10 + B cell generation in HCC and its prospects for clinical application. APPROACH AND RESULTS: TET2 activation in B cells triggered by oxidative stress from the HCC microenvironment promoted IL-10 expression, whereas adoptive transfer of Tet2 -deficient B cells suppressed HCC progression. The aryl hydrocarbon receptor is required for TET2 to hydroxylate Il10 . In addition, high levels of IL-10, TET2, and 5hmc in B cells indicate poor prognosis in patients with HCC. Moreover, we determined TET2 activity using 5hmc in B cells to evaluate the efficacy of anti-programmed death 1 (anti-PD-1) therapy. Notably, TET2 inhibition in B cells facilitates antitumor immunity to improve anti-PD-1 therapy for HCC. CONCLUSIONS: Our findings propose a TET2-dependent epigenetic intervention targeting IL-10 + B cell generation during HCC progression and identify the inhibition of TET2 activity as a promising combination therapy with immune checkpoint inhibitors for HCC.

Linkage-Mediated Electronic Structure Modulation in Multicomponent Covalent Organic Frameworks for Dramatically Promoted Photocatalytic Hydrogen Evolution.

Linkage chemistry is an essential aspect to covalent organic framework (COF) applications; it is highly desirable to precisely modulate electronic structure mediated directly by linkage for efficient COF-based photocatalytic hydrogen evolution, which however, remains substantially challenging. Herein, as a proof of concept, a collection of robust multicomponent pyrene-based COFs with abundant donor-acceptor (D-A) interactions has been judiciously designed and synthesized through molecularly engineering linkage for photogeneration of hydrogen. Controlled locking and conversion of linkage critically contribute to continuously regulating COFs' electronic structures further to optimize photocatalytic activities. Remarkably, the well-modulated optoelectronic properties turn on the average hydrogen evolution rate from zero to 15.67 mmol g-1 h-1 by the protonated quinoline-linked COF decorated with the trifluoromethyl group (TT-PQCOF-CF3). Using diversified spectroscopy and theoretical calculations, we show that multiple modifications toward linkage synergistically lead to the redistribution of charge on COFs with extended π-conjugation and reinforced D-A effect, making TT-PQCOF-CF3 a promising material with significantly boosted carrier separation and migration. This study provides important guidance for the design of high-performance COF photocatalysts based on the strategy of linkage-mediated electronic structure modulation in COFs.

A Broadened Class of Donor-Acceptor Stacked Macrometallacyclic Adducts of Different Coinage Metals.

A yet-outstanding supramolecular chemistry challenge is isolation of novel varieties of stacked complexes with finely-tuned donor-acceptor bonding and optoelectronic properties, as herein reported for binary adducts comprising two different cyclic trinuclear complexes (CTC@CTC'). Most previous attempts focused only on 1-2 factors among metal/ligand/substituent combinations, resulting in heterobimetallic complexes. Instead, here we show that, when all 3 factors are carefully considered, a broadened variety of CTC@CTC' stacked pairs with intuitively-enhanced intertrimer coordinate-covalent bonding strength and ligand-ligand/metal-ligand dispersion are attained (dM-M' 2.868(2) Å; ΔE>50 kcal/mol, an order of magnitude higher than aurophilic/metallophilic interactions). Significantly, CTC@CTC' pairs remain intact/strongly-bound even in solution (Keq 4.67×105 L/mol via NMR/UV-vis titrations), and the gas phase (mass spectrometry revealing molecular peaks for the entire CTC@CTC' units in sublimed samples), rather than simple co-crystal formation. Photo-/electro-luminescence studies unravel metal-centered phosphorescence useful for novel all metal-organic light-emitting diodes (MOLEDs) optoelectronic device concepts. This work manifests systematic design of supramolecular bonding and multi-faceted spectral properties of pure metal-organic macrometallacyclic donor/acceptor (inorganic/inorganic) stacks with remarkably-rich optoelectronic properties akin to well-established organic/organic and organic/inorganic analogues.

Impact of Surface Ligand Identity and Density on the Thermodynamics of H Atom Uptake at Polyoxovanadate-Alkoxide Surfaces.

An understanding of how molecular structure influences the thermodynamics of H atom transfer is critical to designing efficient catalysts for reductive chemistries. Herein, we report experimental and theoretical investigations summarizing structure-function relationships of polyoxovanadate-alkoxides that influence bond dissociation free energies of hydroxide ligands located at the surface of the cluster. We evaluate the thermochemical descriptors of O-H bond strength for a series of clusters, namely [V6O13-x(OH)x(TRIOLR)2]-2 (x = 2, 4, 6; R = NO2, Me) and [V6O11-x(OMe)2(OH)x(TRIOLNO2)2]-2, via computational analysis and open circuit potential measurements. Our findings reveal that modifications to the TRIOL ligand (e.g., changing from the previously reported electron withdrawing nitro-backed ligand to the electron-donating methyl variant) have limited influence on the strength of surface O-H bonds as a result of near complete thermodynamic compensation in these systems (i.e., correlated changes in redox potential and cluster basicity). In contrast, changes in surface density of alkoxide ligands via direct alkoxylation of the polyoxovanadate-alkoxide surface result in measurable increases in bond dissociation free energies of surface O-H bonds for the mixed-valent derivatives. Our findings indicate that the extent of (de)localization of electron density across the cluster core has an impact on the bond dissociation free energies of surface O-H bonds across all oxidation states of the assembly.

Ultrafast Charge Transfer in a Core-shell CdS@Cu-TCPP-Pt Heterojunction for Photocatalytic Hydrogen Production Coupled with Selective Benzylamine Oxidation.

Photocatalytic selective oxidation of organic substances coupled with hydrogen production is believed to be one of the most favorable pathways to make full use of photogenerated charge carriers. However, this catalytic reaction is often discouraged due to the rapid recombination of photogenerated carriers in practical applications. In this work, a core-shell CdS@Cu-TCPP-Pt nanorod heterojunction was dexterously designed for boosting the photocatalytic dehydrogenation performance of benzylamine. The transient absorption results revealed that the photogenerated electron-holes could be effectively separated by properly matching the energy levels in CdS@Cu-TCPP. Surprisingly, Pt embedded in Cu-TCPP not only provided abundant hydrogen production active sites but also facilitated ultrafast charge transfer, which endowed CdS@Cu-TCPP-Pt with remarkable photocatalytic performances for the coproductions of N-benzylidenebenzylamine (1 mL) with a conversion of 23.48% and H2 (20.75 mmol g-1 h-1) under visible irradiation, far surpassing those of CdS and Cu-TCPP. Obviously, the present work verifies that designing and fabricating a hybrid photocatalyst with high separation efficiency of electron-hole pairs is also a significant avenue for other high-performance cooperative dual-functional photocatalytic reactions.

Terpyridine Ni(II) Complex Grafted CdS Nanorods for Cooperative Selective Benzyl Alcohol Oxidation and Hydrogen Production.

Efficient utilization of photogenerated charge carriers to realize photocatalytic solar fuel production and oxidative chemical synthesis is a challenging task. Herein, a conventional amidation reaction route is adopted to successfully construct a novel composite photocatalyst composed of a Ni(II)-terpyridine complex with carboxyl groups grafted on CdS nanorods (labeled as CdS@Ni(terpyC)2). Experimental results have unequivocally revealed that the as-fabricated composite catalyst exhibited a remarkable enhancement in photocatalytic activity for the dehydrogenation of benzyl alcohol under visible light, demonstrating superior hydrogen evolution efficiency and benzaldehyde selectivity, surpassing both pristine CdS and the blend of CdS and Ni(terpyC)2. The carrier dynamics study demonstrated that the Ni(terpyC)2 on the surface of CdS could quickly extract the photogenerated electrons of CdS, which reduced the carrier recombination efficiency, further improving the photocatalytic activity of the catalyst. This work illustrates the effect of surface active site engineering on photocatalysis and is expected to shed substantial inspiration on future surface modulation and design of semiconductor photocatalysts.

Transformation of Metal-Organic Framework from Kinetic to Thermodynamic Product for Controlled Delivery of Vitamin C.

A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5. Furthermore, precise control over VC release can be achieved by introducing surface modifications involving SiO2 onto the structure of VC@HSCT-5, while simultaneously adjusting environmental factors such as pH and temperature conditions. Preliminary cell culture experiments and cytotoxicity assays highlight the biocompatibility of HSTC-5, suggesting that it is a promising platform for sustained drug delivery and diverse biomedical applications.

Does it stable? Intracranial aneurysm wall enhancement might be the warning signals: a meta-analysis of observational studies.

Magnetic resonance vessel wall imaging (MR-VWI) is an emerging imaging technology used to assess the progressive risk of unruptured intracranial aneurysms (UIAs). Unlike the standard evaluation model, MR-VWI is still debatable. This study aims to further define the potential relationship between aneurysm wall enhancement (AWE) and aneurysm stability. Using "intracranial aneurysm", "magnetic resonance", and "enhancement" as keywords, relevant studies were systematically searched in PubMed, Embase, and Cochrane, and the qualified studies were enrolled for further analysis. There were 13 case-control studies, 4 cohort studies, and 2,678 cases of intracranial aneurysms included in the meta-analysis. It was shown that AWE was correlated with intracranial aneurysm rupture (OR = 35.90, 95% CI: 15.58 to 82.75, p < 0.001), growth (OR = 6.69, 95% CI: 2.69 to 16.63, p < 0.001), and presence of symptoms (OR = 14.46, 95% CI: 9.07 to 23.05, p < 0.001). This finding had a high diagnostic value, but the correlation was probably not independent of aneurysm size. The pooled relative risks of the follow-up studies revealed that the risk of UIA progression was approximately 3.33 times higher with AWE than without AWE (RR = 3.33, 95% CI: 2.33 to 4.78, p < 0.001). In addition, the pooled results demonstrated that quantitative indices of VWI enhancement were equally linked with aneurysm stability (OR = 19.61, 95% CI: 10.63 to 36.17, p < 0.001). AWE is an effective imaging method to assess the stability of UIAs, and it can be a marker for the prophylactic treatment of small unruptured intracranial aneurysms in the future, which remains to be validated by prospective studies with large samples.

Strong π-stacking causes unusually large anisotropic thermal expansion and thermochromism.

π-stacking in ground-state dimers/trimers/tetramers of N-butoxyphenyl(naphthalene)diimide (BNDI) exceeds 50 kcal ⋅ mol-1 in strength, drastically surpassing that for the *3[pyrene]2 excimer (∼30 kcal ⋅ mol-1; formal bond order = 1) and similar to other weak-to-moderate classical covalent bonds. Cooperative π-stacking in triclinic (BNDI-T) and monoclinic (BNDI-M) polymorphs effects unusually large linear thermal expansion coefficients (α a , α b , α c , ß) of (452, -16.8, -154, 273) × 10-6 ⋅ K-1 and (70.1, -44.7, 163, 177) × 10-6 ⋅ K-1, respectively. BNDI-T exhibits highly reversible thermochromism over a 300-K range, manifest by color changes from orange (ambient temperature) toward red (cryogenic temperatures) or yellow (375 K), with repeated thermal cycling sustained for over at least 2 y.

Granzyme B Promotes Proliferation, Migration and EMT Process in Gastric Cancer.

Granzyme B (GZMB), a critical member of the Gr gene family, is known to play an essential role in diverse physiological and pathological processes such as inflammation, acute and chronic inflammatory diseases, and cancer progression. In this study, we delve deeper into the role of GZMB within the context of gastric cancer (GC) to examine its expression patterns and functional implications. To accomplish this, we applied a combination of quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry techniques. These methodologies allowed us to accurately gauge GZMB expression levels in GC tissues and investigate their correlation with various clinical-pathological variables. Our secondary focus was to discern the regulatory influence of GZMB on GC cell biology. We used an array of assays including cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine, and migration assays. The effect of GZMB on gastric cancer progression was further validated through a subcutaneous xenograft mouse model. Our findings underscored that GZMB mRNA and protein levels were upregulated in GC tissues, a feature that showed a significant correlation with GC staging. We also discovered that a decrease in GZMB expression via knockdown experiments suppressed the proliferation and migration capabilities of GC cells. This effect was manifested through diminished expression levels of epithelial-mesenchymal transition (EMT) markers. In stark contrast, the overexpression of GZMB through plasmid transfection appeared to enhance the proliferation and migration abilities of GC cells. This was coupled with an upregulation in EMT expression. Our study concludes by emphasizing that GZMB promotes the growth, migration, and EMT processes in gastric cancer. In vitro, cell-based experiments and in vivo xenograft mouse models confirm this. Our findings provide a more comprehensive understanding of GZMB's role in gastric cancer pathogenesis, potentially opening doors for novel therapeutic strategies targeting this molecular pathway.

Linker-Mediated Delocalized Excited States in Dimeric Acceptors Enable Efficient Exciton Dissociation with Negligible Energy-level Offsets.

Efficient exciton dissociation at low energy offsets is key to overcoming voltage losses in organic solar cells. In this work, we developed two dimeric acceptors, i-YT and o-YT, by precisely controlling the position of an asymmetric electron-donating linker. It induced the foldamer conformation of i-YT with a para linkage (relative to the dicyano groups), while retaining the unfold conformation for o-YT. This subtle structural modification influenced the molecular assembly properties, enabled near-zero energy offset exciton dissociation and power conversion efficiencies exceeding 18% for i-YT based organic solar cells. Detailed excitonic dynamics further revealed that the linker position critically influences three processes: the formation of delocalized singlet excited states, ultrafast charge transfer (~5 ps) in solid blends, and the suppression of exciton recombination. Additionally, devices based on i-YT demonstrated outstanding long-term stability, retaining over 85% of their initial efficiency after 1,400 hours of continuous illumination. These findings introduce a new class of dimeric acceptors that combine high efficiency with exceptional stability, offering a promising pathway toward low-energy-loss organic photovoltaics.

Construction of Frustrated Lewis Pairs in Poly(heptazine Imide) Nanosheets via Hydrogen Bonds for Boosting CO2 Photoreduction.

The creation of frustrated Lewis pairs on catalyst surface is an effective strategy for tuning CO2 activation. The critical step in the formation of frustrated Lewis pairs is the spatial effect of proximal Lewis acid-Lewis base pairs. Here, we demonstrate a facile surface functionalization methodology that enables hydrogen bonding between N and H atoms to mediate the construction of frustrated Lewis pairs in poly(heptazine imide), thereby increasing the propensity to activate CO2 molecules. Experimental and theoretical results show that the construction of active hydrogen bonding regions can facilitate the bending of CO2 molecules. Furthermore, the delocalization of electron clouds induced by the hydrogen bonding-mediated frustrated Lewis pairs can promote the heterolytic cleavage and photocatalytic conversion of CO2. This work highlights the potential of utilizing hydrogen bonding-mediated strategy in heterogeneously photocatalytic activation of CO2 over polymer materials.

Building Asymmetric Zn-N3 Bridge between 2D Photocatalyst and Co-catalyst for Directed Charge Transfer toward Efficient H2O2 Synthesis.

Two-dimensional (2D) polymeric semiconductors are a class of promising photocatalysts; however, it remains challenging to facilitate their interlayer charge transfer for suppressed in-plane charge recombination and thus improved quantum efficiency. Although some strategies, such as π-π stacking and van der Waals interaction, have been developed so far, directed interlayer charge transfer still cannot be achieved. Herein, we report a strategy of forming asymmetric Zn-N3 units that can bridge nitrogen (N)-doped carbon layers with polymeric carbon nitride nanosheets (C3N4-Zn-N(C)) to address this challenge. The symmetry-breaking Zn-N3 moiety, which has an asymmetric local charge distribution, enables directed interfacial charge transfer between the C3N4 photocatalyst and the N-doped carbon co-catalyst. As evidenced by femtosecond transient absorption spectroscopy, charge separation can be significantly enhanced by the interfacial asymmetric Zn-N3 bonding bridges. As a result, the designed C3N4-Zn-N(C) catalyst exhibits dramatically enhanced H2O2 photosynthesis activity, outperforming most of the reported C3N4-based catalysts. This work highlights the importance of tailoring interfacial chemical bonding channels in polymeric photocatalysts at the molecular level to achieve effective spatial charge separation.

Highly Diffusive Nonluminescent Carriers in Hybrid Phase Lead Triiodide Perovskite Nanowires.

Crystal structural rearrangements unavoidably introduce defects into materials, where even these small changes in local lattice structure could arouse a prominent impact on the overall nature of crystals. Contrary to the traditional notion that defects obstruct carrier transport, herein, we report a promoted transport mechanism of nonluminescent carriers in single-crystalline CH3NH3PbI3 nanowires (1345.2 cm2 V-1 s-1, about a 14-fold improvement), enabled by the phase transition induced defects (PTIDs). Carriers captured by PTIDs evade both the radiative and non-radiative recombinations during the incomplete tetragonal-to-orthorhombic phase transition at low temperatures, forming a specific nonluminescent state that exhibits an efficient long-distance transport and thereby realize a prominent enhancement of photocurrent responsivity for photodetector applications. The findings provide broader insights into the carrier transport mechanism in perovskite semiconductors and have significant implications for their rational design for photoelectronic applications at varied operating temperatures.

Single-cell landscape and clinical outcomes of infiltrating B cells in colorectal cancer.

B cells constitute a major component of infiltrating immune cells in colorectal cancer (CRC). However, the characteristics of B cells and their clinical significance remain unclear. In this study, using single-cell RNA sequencing and multicolour immunofluorescence staining experiments, we identified five distinct subtypes of B cells with their marker genes, distribution patterns and functional properties in the CRC tumour microenvironment. Meanwhile, we found a higher proportion of IgG plasma cells in tumour sites than that in adjacent normal mucosal tissues. In addition, the CXCL13-producing CD8+ T cells in the tumour tissues could promote the formation of tertiary lymphoid structure (TLS) B cells, and the CCL28-CCR10 axis is pivotal for IgG plasma cell migration from the periphery of TLSs to the tumour stroma. Finally, we identified four distinct colon immune classes (CICs: A-D) and found that CD20+ B cells within TLSs were enriched in one immune-inflamed or hot tumour group (CIC D). This B cell-rich group, which was characterized by strong antigen presentation, IgG plasma cells accumulation, microsatellite instability-high (MSI-H) and high tumour mutation burden (TMB-H), as well as immunosuppressive property in particular, might become a potential predictive biomarker for future immunotherapy. Additionally, in an immunotherapy cohort, patients with the enrichment of B cells and TLSs were demonstrated to obtain significant therapeutic advantages. Together, our findings provide the detailed landscape of infiltrating B cells and their potential clinical significance in CRC.