Inhibiting the NADase CD38 improves cytomegalovirus-specific CD8+ T cell functionality and metabolism.

Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in immunocompromised individuals such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in immunosuppressed individuals have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in immunocompromised patients and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with non-controlled CMV infection. These dysregulations comprise impaired glycolysis and increased mitochondrial stress, which is associated with an intensified expression of the nicotinamide adenine dinucleotide nucleotidase (NADase) CD38. Inhibiting NADase activity of CD38 reinvigorated the metabolism and improved cytokine production of CMV-specific CD8+ T cells. These findings were corroborated in a mouse model of CMV infection under conditions of immunosuppression. Thus, dysregulated metabolic states of CD8+ T cells could be targeted by inhibiting CD38 to reverse hypo-responsiveness in individuals who fail to control chronic viral infection.

Undescribed polyketides from endophytes associated with the critically endangered conifer Abies beshanzuensis.

Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 µg/mL, respectively.

Zinc finger protein 180 induces an apoptotic phenotype by activating METTL14 transcriptional activity in colorectal cancer.

Zinc finger protein 180 (ZNF180) is a multifunctional protein that interacts with nucleic acids and regulates various cellular processes; however, the function of ZNF180 in colorectal cancer (CRC) remains unclear. The present study investigated the role and function of ZNF180 in CRC, and aimed to reveal the underlying molecular mechanism. The results revealed that ZNF180 was downregulated in CRC tissues and was associated with a good prognosis in patients with CRC. Additionally, the expression of ZNF180 was downregulated by methylation in CRC. In vivo and in vitro experiments revealed that ZNF180 overexpression was functionally associated with the inhibition of cell proliferation and the induction of apoptosis. Mechanistically, chromatin immunoprecipitation­PCR and luciferase assays demonstrated that ZNF180 markedly regulated the transcriptional activity of methyltransferase 14, N6­adenosine­methyltransferase non­catalytic subunit (METTL14) by directly binding to and activating its promoter region. Simultaneous overexpression of ZNF180 and knockdown of METTL14 indicated that the reduction of METTL14 could suppress the effects of ZNF180 on the induction of apoptosis. Clinically, the present study observed a significant positive correlation between ZNF180 and METTL14 expression levels, and low expression of ZNF180 and METTL14 predicted a poor prognosis in CRC. Overall, these findings revealed a novel mechanism by which the ZNF180/METTL14 axis may modulate apoptosis and cell proliferation in CRC. This evidence suggests that this axis may serve as a prognostic biomarker and therapeutic target in patients with CRC.

HMGA1 promotes the progression of esophageal squamous cell carcinoma by elevating TKT-mediated upregulation of pentose phosphate pathway.

Esophageal squamous cell carcinoma (ESCC) possesses a poor prognosis and treatment outcome. Dysregulated metabolism contributes to unrestricted growth of multiple cancers. However, abnormal metabolism, such as highly activated pentose phosphate pathway (PPP) in the progression of ESCC remains largely unknown. Herein, we report that high-mobility group AT-hook 1 (HMGA1), a structural transcriptional factor involved in chromatin remodeling, promoted the development of ESCC by upregulating the PPP. We found that HMGA1 was highly expressed in ESCC. Elevated HMGA1 promoted the malignant phenotype of ESCC cells. Conditional knockout of HMGA1 markedly reduced 4-nitroquinoline-1-oxide (4NQO)-induced esophageal tumorigenesis in mice. Through the metabolomic analysis and the validation assay, we found that HMGA1 upregulated the non-oxidative PPP. With the transcriptome sequencing, we identified that HMGA1 upregulated the expression of transketolase (TKT), which catalyzes the reversible reaction in non-oxidative PPP to exchange metabolites with glycolytic pathway. HMGA1 knockdown suppressed the PPP by downregulating TKT, resulting in the reduction of nucleotides in ESCC cells. Overexpression of HMGA1 upregulated PPP and promoted the survival of ESCC cells by activating TKT. We further characterized that HMGA1 promoted the transcription of TKT by interacting with and enhancing the binding of transcription factor SP1 to the promoter of TKT. Therapeutics targeting TKT with an inhibitor, oxythiamine, reduced HMGA1-induced ESCC cell proliferation and tumor growth. Together, in this study, we identified a new role of HMGA1 in ESCCs by upregulating TKT-mediated activation of PPP. Our results provided a new insight into the role of HMGA1/TKT/PPP in ESCC tumorigenesis and targeted therapy.

A visible-light regulated luminescent switch based on a spiropyran-derived Pt(II) complex for advanced anti-counterfeiting materials.

A dual optical switch regulated by visible light has been developed through an integrated strategy, including luminescent Pt(II) and photochromic spiropyran (SP) as a triplet-sensitizer and photo-regulator building block, respectively. An efficient Förster resonance energy transfer (FRET) process is achieved, along with apparent and emissive color changes under visible light irradiation and temperature stimuli, which was utilized to develop advanced anti-counterfeiting materials.

Californium-252 Intracavitary Radiotherapy for Primary Vaginal Carcinoma: A Retrospective Clinical Study.

Objective: To investigate the therapeutic effect of Cf-252 neutron intracavitary brachytherapy (ICBT) in the treatment of primary vaginal carcinoma of stage I-III, along with advanced complications. Methods: Between August 2009 and August 2013, 41 patients with intact primary vaginal carcinoma based on the histological diagnosis at the Second Cancer Hospital of Heilongjiang Province (Beidahuang Group General Hospital) and the Daping Hospital of the Third Military Medical University were included in this study. Among them, 32 patients were squamous cell carcinoma, and 9 adenocarcinomas. Stage I patients were treated with ICBT alone. Patients at stages II and III were treated using ICBT combined with external beam radiotherapy (EBRT). Results: The mean age, the rate of the 5-year local control, the rate of the 5-year overall survival was increased. The rate of the 5-year tumor-free survival was 56.1%, and the incidence of advanced serious complications (grade II and above radiation cystitis, proctitis, etc.) was 29.3%. Compared to later stages, early-stage patients are in better physical shape, so they are better able to withstand the toxic side effects of treatment. The local control (LC), overall survival (OS), or disease-free survival (DFS) rate in stage III patients was significantly lower than those in stage I and stage II. The rate of OS in stage I patients was 90.9% (10/11), which was significantly higher than that in all patients (56.1%; 23/41). Moreover, the mean survival time was significantly different between stage III and stage I. In addition, the survival status of squamous cell carcinoma and adenocarcinoma was also very different. Conclusion: In summary, the use of Cf-252 ICBT radiotherapy resulted in a higher rate of local control of vaginal cancer and a lower rate of recurrence, better-shrinking effect, and efficacy for advanced tumors, and has clinical prospects.

Precise Regulation the Multiemission Based on Soft Double Salt for Information Encryption.

Manipulation of multiemissive luminophores is meaningful for exploring luminescent materials. Herein, we report a soft double salt assembly strategy that could result in well-organized nanostructures and different luminescence based on multiple weak intermolecular interactions thanks to the existence of electrostatic attraction between the anionic and cationic platinum(II) complexes. The cationic complexes B1 and B2 can coassemble with anionic complex A, respectively, and the emission switches from monomeric and excimeric emission to the triplet metal-metal-to-ligand charge transfer (3MMLCT) along with morphology changes from 0-dimensional (0-D) nanospheres to 3-dimensional (3-D) nanostructures. It is demonstrated that an isodesmic growth mechanism is adopted during the spontaneous self-assembly process, and the relative negative ΔG values make the anionic and cationic complex molecules prefer to form aggregates based on π-π stacking, Pt···Pt interactions, and electrostatic interactions. The coassembly strategy between anionic and cationic complexes endows them with multicolor luminescent and apparent color as optical materials for advanced information encryption.

Dietary Selenium Insufficiency Induces Cardiac Inflammatory Injury in Chicks.

BACKGROUND: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency. OBJECTIVES: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life. METHODS: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway. RESULTS: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1ß), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks. CONCLUSIONS: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB.

HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

Trapping of microplastics and other anthropogenic particles in seagrass beds: Ubiquity across a vertical and horizontal sampling gradient.

Seagrass beds can trap large amounts of marine debris leading to areas of accumulation, known as 'sinks', of anthropogenic particles. While the presence of vegetation can enhance accumulation, less is known about how the trapping effect changes from vegetated to less vegetated patches. To test this, vegetation and sediment were sampled along a vegetation percent cover gradient from the centre of seagrass beds to nearby less vegetated patches. To determine whether trapped particles can lead to increased accumulation in associated fauna, gastropods were also collected from the transects laid across this gradient. Extracted anthropogenic particles were counted and characterised. Particles were detected in all sample types and reached quantifiable limits in at least 50% of sediment and gastropod samples. There was no significant difference in the distribution of particles found in seagrass beds compared to less vegetated patches, suggesting other factors contribute to the trapping efficiency of biogenic habitats besides simply the presence or absence of vegetation.

Reproductive toxicity of cadmium stress in male animals.

Cadmium (Cd) is a common heavy metal pollutant in the environment, and the widespread use of products containing Cd compounds in industry has led to excessive levels in the environment, which enter the animal body through the food chain, thus seriously affecting the reproductive development of animals. Related studies have reported that Cd severely affects spermatogonia development and spermatogenesis in animals. In contrast, the reproductive toxicity of Cd in males and its mechanism of action have not been clarified. Therefore, this paper reviewed the toxic effects of Cd on germ cells, spermatogonia somatic cells and hypothalamic-pituitary-gonadal axis (HPG axis) of male animals and its toxic action mechanisms of oxidative stress, apoptosis and autophagy from the perspectives of cytology, genetics and neuroendocrinology. The effects of Cd stress on epigenetic modification of reproductive development in male animals were also analyzed. We hope to provide a reference for the in-depth study of the toxicity of Cd on male animal reproduction.

How to assess the long-term recovery outcomes of patients with cauda equina syndrome before surgery: a retrospective cohort study.

BACKGROUND: Factors influencing recovery after decompression surgery for cauda equina syndrome (CES) are not completely identified. The authors aimed to investigate the most valuable predictors (MVPs) of poor postoperative recovery (PPR) in patients with CES and construct a nomogram for discerning those who will experience PPR. METHODS: Three hundred fifty-six patients with CES secondary to lumbar degenerative diseases treated at Xijing Hospital were randomly divided into training ( N =238) and validation ( N =118) cohorts at a 2:1 ratio. Moreover, 92 patients from the 970 th Hospital composed the testing cohort. Least Absolute Shrinkage and Selection Operator regression (LASSO) was used for selecting MVPs. The nomogram was developed by integrating coefficients of MVPs in the logistic regression, and its discrimination, calibration, and clinical utility were validated in all three cohorts. RESULTS: After 3 to 5 years of follow-up, the residual rates of bladder dysfunction, bowel dysfunction, sexual dysfunction, and saddle anesthesia were 41.9, 44.1, 63.7, and 29.0%, respectively. MVPs included stress urinary incontinence, overactive bladder, low stream, difficult defecation, fecal incontinence, and saddle anesthesia in order. The discriminatory ability of the nomogram was up to 0.896, 0.919, and 0.848 in the training, validation, and testing cohorts, respectively. Besides, the nomogram showed good calibration and clinical utility in all cohorts. Furthermore, the optimal cutoff value of the nomogram score for distinguishing those who will experience PPR was 148.02, above which postoperative outcomes tend to be poor. CONCLUSION: The first pretreatment nomogram for discerning CES patients who will experience PPR was developed and validated, which will aid clinicians in clinical decision-making.

Clinical application of middle descending colon-double lumen ostomy with distal stoma narrowing in the treatment of anorectal malformation.

BACKGROUND: Anorectal malformations (ARMs) are the most common congenital anomaly of the digestive tract. And colostomy should be performed as the first-stage procedure in neonates diagnosed with intermediate- or high-type ARMs. However, the most classic Pe˜na's colostomy still has some disadvantages such as complicated operation procedure, susceptibility to infection, a greater possibility of postoperative incision dehiscence, difficulty of nursing and large surgical trauma and incision scarring when closing the stoma. We aimed to explore the effectiveness of middle descending colon-double lumen ostomy (MDCDLO) in the treatment of high and intermediate types of anorectal malformations. METHODS: We retrospectively reviewed the data of patients who underwent MDCDLO for high or intermediate types of ARMs between June 2016 and December 2021 in our hospital. The basic characteristics were recorded. All patients were followed up monthly to determine if any complication happen. RESULTS: There were 17 boys and 6 girls diagnosed with high or intermediate types of ARMs in our hospital between June 2016 and December 2021. All 23 patients were cured without complications such as abdominal incision infection, stoma stenosis, incisional hernia, and urinary tract infection in the postoperative follow-up time of 6 months to 6 years except one case of proximal intestinal prolapse was restored under anesthesia. CONCLUSION: MDCDLO offers the advantages of simplicity, efficiency, safety, mild trauma, and small scarring in the treatment of high and intermediate types of anorectal malformations.

CD4+ T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors.

CD4+ T cells can "help" or "license" conventional type 1 dendritic cells (cDC1s) to induce CD8+ cytotoxic T lymphocyte (CTL) anticancer responses, as proven in mouse models. We recently identified cDC1s with a transcriptomic imprint of CD4+ T-cell help, specifically in T-cell-infiltrated human cancers, and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy. Here, we delineate the mechanism of cDC1 licensing by CD4+ T cells in humans. Activated CD4+ T cells produce IFNß via the STING pathway, which promotes MHC-I antigen (cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses. In cooperation with CD40 ligand (L), IFNß also optimizes the costimulatory and other functions of cDC1s required for CTL response induction. IFN-I-producing CD4+ T cells are present in diverse T-cell-infiltrated cancers and likely deliver "help" signals to CTLs locally, according to their transcriptomic profile and colocalization with "helped/licensed" cDCs and tumor-reactive CD8+ T cells. In agreement with this scenario, the presence of IFN-I-producing CD4+ T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

Optical Variation and Molecular Transformation of Brown Carbon During Oxidation by NO3• in the Aqueous Phase.

The NO3•-driven nighttime aging of brown carbon (BrC) is known to greatly impact its atmospheric radiative forcing. However, the impact of oxidation by NO3• on the optical properties of BrC in atmospheric waters as well as the associated reaction mechanism remain unclear. In this work, we found that the optical variation of BrC proxies under environmentally relevant NO3• exposure depends strongly on their sources, with enhanced light absorptivity for biomass-burning BrC but bleaching for urban aerosols and humic substances. High-resolution mass spectrometry using FT-ICR MS shows that oxidation by NO3• leads to the formation of light-absorbing species (e.g., nitrated organics) for biomass-burning BrC while destroying electron donors (e.g., phenols) within charge transfer complexes in urban aerosols and humic substances, as evidenced by transient absorption spectroscopy and NaBH4 reduction experiments as well. Moreover, we found that the measured rate constants between NO3• with real BrCs (k = (1.8 ± 0.6) × 107 MC-1s-1, expressed as moles of carbon) are much higher than those of individual model organic carbon (OC), suggesting the reaction with OCs may be a previously ill-quantified important sink of NO3• in atmospheric waters. This work provides insights into the kinetics and molecular transformation of BrC during the oxidation by NO3•, facilitating further evaluation of BrC's climatic effects and atmospheric NO3• levels.

HMGA1 drives chemoresistance in esophageal squamous cell carcinoma by suppressing ferroptosis.

Chemotherapy is a primary treatment for esophageal squamous cell carcinoma (ESCC). Resistance to chemotherapeutic drugs is an important hurdle to effective treatment. Understanding the mechanisms underlying chemotherapy resistance in ESCC is an unmet medical need to improve the survival of ESCC. Herein, we demonstrate that ferroptosis triggered by inhibiting high mobility group AT-hook 1 (HMGA1) may provide a novel opportunity to gain an effective therapeutic strategy against chemoresistance in ESCC. HMGA1 is upregulated in ESCC and works as a key driver for cisplatin (DDP) resistance in ESCC by repressing ferroptosis. Inhibition of HMGA1 enhances the sensitivity of ESCC to ferroptosis. With a transcriptome analysis and following-up assays, we demonstrated that HMGA1 upregulates the expression of solute carrier family 7 member 11 (SLC7A11), a key transporter maintaining intracellular glutathione homeostasis and inhibiting the accumulation of malondialdehyde (MDA), thereby suppressing cell ferroptosis. HMGA1 acts as a chromatin remodeling factor promoting the binding of activating transcription factor 4 (ATF4) to the promoter of SLC7A11, and hence enhancing the transcription of SLC7A11 and maintaining the redox balance. We characterized that the enhanced chemosensitivity of ESCC is primarily attributed to the increased susceptibility of ferroptosis resulting from the depletion of HMGA1. Moreover, we utilized syngeneic allograft tumor models and genetically engineered mice of HMGA1 to induce ESCC and validated that depletion of HMGA1 promotes ferroptosis and restores the sensitivity of ESCC to DDP, and hence enhances the therapeutic efficacy. Our finding uncovers a critical role of HMGA1 in the repression of ferroptosis and thus in the establishment of DDP resistance in ESCC, highlighting HMGA1-based rewiring strategies as potential approaches to overcome ESCC chemotherapy resistance. Schematic depicting that HMGA1 maintains intracellular redox homeostasis against ferroptosis by assisting ATF4 to activate SLC7A11 transcription, resulting in ESCC resistance to chemotherapy.

Surface Lattice Modulation Enables Stable Cycling of High-Loading All-solid-state Batteries at High Voltages.

Halide solid electrolytes, known for their high ionic conductivity at room temperature and good oxidative stability, face notable challenges in all-solid-state Li-ion batteries (ASSBs), especially with unstable cathode/solid electrolyte (SE) interface and increasing interfacial resistance during cycling. In this work, we have developed an Al3+-doped, cation-disordered epitaxial nanolayer on the LiCoO2 surface by reacting it with an artificially constructed AlPO4 nanoshell; this lithium-deficient layer featuring a rock-salt-like phase effectively suppresses oxidative decomposition of Li3InCl6 electrolyte and stabilizes the cathode/SE interface at 4.5 V. The ASSBs with the halide electrolyte Li3InCl6 and a high-loading LiCoO2 cathode demonstrated high discharge capacity and long cycling life from 3 to 4.5 V. Our findings emphasize the importance of specialized cathode surface modification in preventing SE degradation and achieving stable cycling of halide-based ASSBs at high voltages.

Location matters: spatial dynamics of tumor-infiltrating T cell subsets is prognostic in colon cancer.

Background: Colon cancer is a heterogeneous disease and consists of various molecular subtypes. Despite advances in high-throughput expression profiling, limitations remain in predicting clinical outcome and assigning specific treatment to individual cases. Tumor-immune interactions play a critical role, with tumors that activate the immune system having better outcome for the patient. The localization of T cells within tumor epithelium, to enable direct contact, is essential for antitumor function, but bulk DNA/RNA sequencing data lacks spatial distribution information. In this study, we provide spatial T cell tumor distribution and connect these data with previously determined genomic data in the AC-ICAM colon cancer patient cohort. Methods: Colon cancer patients (n=90) with transcriptome data available were selected. We used a custom multiplex immunofluorescence assay on colon tumor tissue sections for quantifying T cell subsets spatial distribution in the tumor microenvironment, in terms of cell number, location, mutual distance, and distance to tumor cells. Statistical analyses included the previously determined Immunologic Constant of Rejection (ICR) transcriptome correlation and patient survival, revealing potential prognostic value in T cell spatial distribution. Results: T cell phenotypes were characterized and CD3+CD8-FoxP3- T cells were found to be the predominant tumor-infiltrating subtype while CD3+FoxP3+ T cells and CD3+CD8+ T cells showed similar densities. Spatial distribution analysis elucidated that proliferative T cells, characterized by Ki67 expression, and Granzyme B-expressing T cells were predominantly located within the tumor epithelium. We demonstrated an increase in immune cell density and a decrease in the distance of CD3+CD8+ T cells to the nearest tumor cell, in the immune active, ICR High, immune subtypes. Higher densities of stromal CD3+FoxP3+ T cells showed enhanced survival outcomes, and patients exhibited superior clinical benefits when greater spatial distances were observed between CD3+CD8-FoxP3- or CD3+CD8+ T cells and CD3+FoxP3+ T cells. Conclusion: Our study's in-depth analysis of the spatial distribution and densities of major T cell subtypes within the tumor microenvironment has provided valuable information that paves the way for further research into the intricate relationships between immune cells and colon cancer development.