Dendritic Cells Research Articles

UDP-glucose Regulates Dendritic Cell Mitochondrial Respiration via a Nitric Oxide-Dependent Mechanism.

Bone marrow-derived dendritic cell (BMDC) activation is associated with rewiring of cellular metabolism and concurrent large-scale changes in gene expression promoting a pro-inflammatory program characterized by expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO). NO inhibits vital cellular activities including mitochondrial respiration. Mitochondrial respiration inhibition via NO occurs at discrete levels of activating stimulus, termed the mitochondrial respiration threshold, and regulation of this threshold is not fully understood. In this work, we characterize the role of UDP-glucose as a modulator of NO-mediated mitochondrial respiration inhibition via P2Y14 receptor signaling in stimulated BMDCs. We demonstrate BMDCs exhibit an enhanced pro-inflammatory profile in the presence of UDP-glucose, providing evidence for a new NO-regulatory axis in BMDCs. These studies highlight the importance of the growing body of literature supporting metabolites as signaling molecules in activating conditions thus allowing for better modeling of physiologically-relevant contexts for myeloid cell encounters with microbial stimuli.

Early T-precursor acute lymphoblastic leukemia with mature plasmacytoid dendritic cell proliferation.

Early T-precursor acute lymphoblastic leukemia with mature plasmacytoid dendritic cell proliferation.

Efficient generation of human dendritic cells from iPSC by introducing a feeder-free expansion step for hematopoietic progenitors.

Dendritic cells (DCs) are rare innate immune cells that are essential regulators of anti-tumour, anti-viral and vaccine responses by the adaptive immune system. Conventional dendritic cells, particularly the cDC1 subset, are most desired for DC-based immunotherapies, however, it can be difficult to isolate sufficient numbers of primary cells from patients. The most common alternate sources of DC are ex vivo monocyte-derived DC, although patient-derived monocytes are often dysfunctional. Induced pluripotent stem cells (iPSC) offer a promising solution, providing an opportunity for in vitro generating DCs that are suitable for allogenic off-the-shelf batch-manufactured cells. Here, we developed an in vitro protocol designed to maximise the yield of iPSC-derived DC progenitors, with the specific goal of generating cDC1-like cells. The iPSC-DCs subsets generated by our method could be partitioned by cell surface phenotypes of cDC1, cDC2 and DC3, but they were most transcriptionally similar to monocyte-derived DC (MoDC). Stimulated iPSC-DCs generated pro-inflammatory cytokines, expressed migratory chemokine receptors including CCR7, upregulated co-stimulatory molecules and induced the proliferation of CD4/CD8 T-cells. Altogether these data indicate that iPSC-derived DC have the potential to traffic through lymphatic endothelium and engage productively with T-cells. This method offers a promising step towards an expandable source of allogeneic human dendritic cells for future applications.

Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells

Squalene-based emulsion (SE) adjuvants like MF59 and AS03 are used in protein subunit vaccines against influenza virus (e.g., Fluad, Pandemrix, Arepanrix) and SARS-CoV-2 (e.g., Covifenz, SKYCovione). We demonstrate the critical role of uric acid (UA), a damage-associated molecular pattern (DAMP), in triggering immunogenicity by SE adjuvants. In mice, SE adjuvants elevated DAMP levels in draining lymph nodes. Strikingly, inhibition of UA synthesis reduced vaccine-induced innate immunity, subsequently impairing optimal antibody and T cell responses. In vivo treatment with UA crystals elicited partial adjuvant effects. In vitro stimulation with UA crystals augmented the activation of dendritic cells (DCs) and B cells and altered multiple pathways in these cells, including inflammation and antigen presentation in DCs and cell proliferation in B cells. In an influenza vaccine model, UA contributed to protection against influenza viral infection. These results demonstrate the importance of DAMPs, specifically the versatile role of UA in the immunogenicity of SE adjuvants, by regulating DCs and B cells.

Chiral Aluminum Oxyhydroxide Supraparticles as Adjuvants.

Aluminum-based adjuvants dominate global vaccine formulations owing to their proven efficacy in humoral immunity induction. However, their inherent limitations in activating cellular immunity pose critical challenges for vaccine development. In this study, chiral flower-like aluminum oxyhydroxide (AlOOH) supraparticles (SPs) are synthesized via a one-pot hydrothermal method using cysteine (Cys) enantiomers as chiral ligands, achieving a g-factor of 0.004. L-AlOOH SPs (L-SPs) demonstrate significantly greater enhancement in dendritic cell (DC) maturation and antigen cross-presentation efficiency compared to D-AlOOH SPs (D-SPs), indicating its potential as an adjuvant. Mechanistic studies reveal that L-SPs enter DCs via Toll-like receptor 2 (TLR2), thereby enhancing NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation. In vivo experiments show that L-SPs generate 21.59-fold higher OVA-specific antibody titers than commercial aluminum adjuvants. Further studies show that L-SPs, after mixed with H9N2 virus proteins, enhance influenza virus antibody titers by 15.28-fold, with sustained protection, confirming its translational potential. This study demonstrates the performance of chiral AlOOH SPs to simultaneously amplify humoral and cellular immunological responses, entering it as a promising next-generation adjuvant for cancer immunotherapy and pandemic preparedness.

Anti-tumor immunity mediated by engineered allogeneic stem cells exploiting TRAIL-induced cell death and FLT3L immunomodulation.

Death receptor (DR)-targeted therapies offer a promising tumor cell-specific therapeutic strategy for highly malignant brain tumors, such as glioblastoma (GBM). However, whether DR-mediated cell death leads to activation of the adaptive immune system and impacts the tumor immune microenvironment (TIME) remains unknown. In this study we explored the 1) immunomodulatory role of secretable human DR4/5 ligand, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (S-TRAIL); and 2) the therapeutic potential of allogeneic stem cells (SCs) delivered S-TRAIL and myeloid progenitor cell activating cytokine, FMS-like tyrosine kinase 3 ligand (FLT3L). We created syngeneic murine immune -active and -suppressive mouse GBM tumor models expressing a human-murine chimeric DR5. Next, we created therapeutic SCs that release FLT3L and S-TRAIL and assessed their efficacy in GBM tumor models. To facilitate clinical translation, we tested the mechanism-based efficacy of encapsulated SC-TRAIL/FLT3L in both syngeneic and humanized mouse tumor-models of GBM-resection. We show that S-TRAIL induced apoptosis in GBM cells provokes infiltration and maturation of dendritic cells (DC) within the TIME in vivo. Next, we show that local transplantation of encapsulated bimodal SCs post-surgical GBM-resection improves the survival probability and induces upregulation of conventional DC type 1 (cDC1) and CD8+ T cells. Furthermore, treatment with encapsulated off-the-shelf clinical-grade bimodal human SCs in GBM-bearing humanized mice results in a significant decrease in tumor-volumes. This study uncovers the immunological role of TRAIL-mediated cell death in the TIME and provides evidence for the encapsulated cell-based therapy to kill residual tumor-cells and induce long-term immunity.

The Effect of Autologous Dendritic Cell Therapy on Renal Perfusion in Diabetic Kidney Disease: Analysis of Doppler Ultrasound and Angiogenesis Biomarkers

The Effect of Autologous Dendritic Cell Therapy on Renal Perfusion in Diabetic Kidney Disease: Analysis of Doppler Ultrasound and Angiogenesis Biomarkers

Spontaneous Induced Cascade targeting biomimetic nanoparticles to inhibit dendritic cell maturation for ameliorating atherosclerosis and MRI

Spontaneous Induced Cascade targeting biomimetic nanoparticles to inhibit dendritic cell maturation for ameliorating atherosclerosis and MRI

Preventing the antigen-presenting function of retinal microglia blocks autoimmune neuroinflammation by dendritic cell-primed CD4+ T cells.

Preventing the antigen-presenting function of retinal microglia blocks autoimmune neuroinflammation by dendritic cell-primed CD4+ T cells.

Decoding the causal association between immune cells and three chronic respiratory diseases: Insights from a bi-directional Mendelian randomization study

BackgroundNumerous studies have indicated the correlations of immune traits and chronic respiratory diseases (CRDs). Whereas, causality is still implicative. Hence, our study was designed to investigate the causal relations utilizing bidirectional Mendelian randomization (MR) and to identify the immune traits of potential significance.MethodsUsing GWAS datasets, we performed Mendelian randomization (MR) analyses to examine 731 immune traits associated with three CRDs: asthma, bronchiectasis and chronic obstructive pulmonary disease (COPD). Six widely applied MR approaches, along with Bayesian weighted Mendelian randomization analysis, were utilized to assess causality. Through extensive sensitivity assessments, heterogeneity and pleiotropy have been examined. For integrity, leave-one-out analysis was implemented as the final step.ResultsOur study reveals 13 immune traits that may have a genetic basis for predicting the occurrence of CRDs, which include two risk traits (CD62L− myeloid dendritic cell (DC) absolute count (AC), CD8 on CD28+ CD45RA− CD8+ T cell) and four protective traits (CD39+ CD8+ %T cell, CD4 on CD39+ activated CD4 regulatory T (Treg) cell, herpes virus entry mediator (HVEM) on Central Memory (CM) CD8+ T cell, CD16 on CD14+ CD16+ monocyte) in COPD, three protective traits (IgD− CD27− %B cell, CD3 on CM CD8+ T cell, CD16 on CD14+ CD16+ monocyte) and one risk trait (CD62L− %DC) in bronchiectasis. Additionally, two risk traits (CD14− CD16− AC monocyte, CD19 on IgD+ CD38+ B cell) and one protective trait (HVEM on CD45RA− CD4+ T cell) were identified in asthma. Sensitivity analyses showed no indications of pleiotropy or signs of heterogeneity. The inverse MR assessment results gave no evidence of reverse causations, ultimately validating the soundness of the findings.ConclusionsOur investigation identifies latent correlations of immune traits and three major CRDs, offering novel perspectives on the preventive and therapeutical strategies for CRDs.Graphical abstract

Unveiling cellular communications through rapid pan-membrane-protein labeling

Dynamic protein distribution within and across the plasma membrane is pivotal in regulating cell communication. However, rapid, high-density labeling methods for multiplexed live imaging across diverse cell types remain scarce. Here, we demonstrate N-hydroxysuccinimide (NHS)-ester-based amine crosslinking of fluorescent dyes to uniformly label live mammalian cell surface proteins. Using model cell systems, we capture previously elusive membrane topology and cell-cell interactions. Live imaging shows transient membrane protein accumulation at cell-cell contacts and bidirectional migration patterns guided by membrane fibers in DC2.4 dendritic cells. Multiplexed superresolution imaging reveals the biogenesis of membrane tunneling nanotubes that facilitate intercellular transfer in DC2.4 cells, and caveolin 1-dependent endocytosis of insulin receptors in HEK293T cells. 3D superresolution imaging reveals membrane topology remodeling in response to stimulation, generation of microvesicles, and phagocytic activities in Jurkat T cells. Furthermore, NHS-labeling remains stable in vivo, enabling visualization of intercellular transfer among splenocytes using a T cell lymphoma mouse model.

SLAMF7 and SLAMF8 receptors shape human plasmacytoid dendritic cell responses to intracellular bacteria.

Plasmacytoid dendritic cells (pDCs), professional type I IFN-producing cells, have been implicated in host responses against bacterial infections. However, their role in host defense is debated, and the operating molecular mechanisms are unknown. Certain signaling lymphocyte activation molecule family (SLAMF) members act as microbial sensors and modulate immune functions in response to infection. Here, human blood transcriptomic analyses reveal the involvement of SLAMF7 and SLAMF8 in many infectious diseases, with elevated levels associated with type I IFN responses in salmonellosis and brucellosis patients. We further identify SLAMF7 and SLAMF8 as key regulators of human pDC function. They activate pDC maturation and cytokine production during infection with bacteria that induce acute (Salmonella) or chronic (Brucella) inflammation. SLAMF7 and SLAMF8 signal through NF-κB, IRF7, and STAT-1, and limit mitochondrial ROS accumulation upon Salmonella infection. Remarkably, this SLAMF7/8-dependent control of mitochondrial ROS levels favors bacterial persistence and NF-κB activation. Overall, our results unravel essential shared multifaceted roles of SLAMF7 and SLAMF8 in finely tuning human pDC responses to intracellular bacterial infections with potential for future diagnostic and therapeutic applications.

Selenium-Binding Protein 1-Deficient Dendritic Cells Protect Mice from Sepsis by Increased Treg/Th17

Selenium-binding protein 1 (SELENBP1) has been implicated in cancer development, neurological disorders, tissue injury, metabolic regulation, and cell differentiation. Sepsis is characterized prominently by immunological dysregulation and severe organ damage. However, whether SELENBP1 improves sepsis by regulating immune cell activity remains unknown. Here, we detected an elevation of SELENBP1 levels in the blood of sepsis patients and in the livers of septic mice. Significantly, SELENBP1 knockout (KO) prolonged survival in septic mice. This phenomenon was accompanied by decreased liver damage, reduced inflammation levels, and an increased regulatory T cell/T helper 17 cell (Treg/Th17) ratio in the spleen. Additionally, SELENBP1 deficiency induced a redox imbalance and inhibited dendritic cell (DC) maturation, resulting in a tolerogenic DC (tolDC) phenotype and an increase in the Treg/Th17 ratio. Furthermore, SELENBP1-KO mature DCs (mDCs) alleviated liver injury by increasing the Treg/Th17 ratio in the spleen, thus improving the survival of septic mice. These findings indicate that SELENBP1 is involved in sepsis by regulating DC immune activity, which might provide a potential way for sepsis treatment.

ICAM-1/CD18-mediated sequestration of parasitized phagocytes in cortical capillaries promotes neuronal colonization by Toxoplasma gondii

Microbial translocation across the blood-brain barrier (BBB) is a prerequisite for colonization of the central nervous system. The obligate intracellular parasite Toxoplasma gondii chronically infects the brain parenchyma of humans and animals, in a remarkably stealthy fashion. We investigated the mechanisms of BBB traversal by T. gondii (genotypes I, II, III) and T. gondii-infected leukocytes, using intracarotid arterial delivery into the cerebral circulation of mice. Unexpectedly, parasitized dendritic cells (DCs) and other peripheral blood mononuclear cells were found to persistently sequester within cortical capillaries. Post-replicative egress of T. gondii from sequestered DCs was followed by rapid parasite localization within cortical neurons. Infection-induced microvascular inflammation dramatically elevated the sequestration of parasitized DCs, while treatments targeting the ICAM-1/CD18 leukocyte adhesion axis with blocking antibodies strongly reverted sequestration. The parasite effectors TgWIP and GRA15, known to promote leukocyte hypermigration and inflammatory activation, further increased both the capillary sequestration of infected DCs and cerebral parasite loads in a strain-dependent manner. These findings reveal that the sequestration of parasitized leukocytes in cortical capillaries, with subsequent BBB traversal following parasite egress, provides a mechanism for T. gondii’s rapid access to cortical neurons during primary infection.

Molecular basis identification and hypnotic drug interactions for cognitive impairment related to sleep deprivation

Chronic sleep deprivation can lead to cognitive impairment which makes it difficult to think, focus, and make comprehensive decisions. This in turn leads to the progression and increased risk of several diseases. This study aimed to explore potential drug targets and biomarkers underlying the increased disease risk due to sleep deprivation, including stress responses, immune dysfunction, and metabolic dysregulation. Four datasets namely GSE40562, GSE98566, GSE98582 for sleep deprivation, and GSE26576 normal brain cells were utilized to understand the molecular basis and potential drug targets associated with sleep deprivation. The GEO2R tool, Robust rank aggregations, and Venny were used to retrieve the common DEGs. Functional gene and pathway analyses were carried out via GO and the KEGG analyses. The STRING and CytoHuba plugins were utilized to identify the protein-protein interactions (PPIs) as well as the hub genes in the main PPI subnetworks following the drug interaction of the hub genes and GEPIA-based survival analysis of the DEGs. A total of 160 common DEGs were retrieved from all four datasets. Among them, 65 were down-regulated and 95 were up-regulated. TOP2A, AURKB, NEFL, CDC42, ASPM, GAP43, PVALB, NUF2, CALM1, TPR, KIF5B, KIF15, TROAP, NDC80, PBK, MKI67, SST, AHSP, ALAS2, and NEFH were retrieved as hub genes. While based on drug interaction, survival analysis and gene expression profile eight hub gene named TOP2A, AURKB, PVALB, CALM1, KIF5B, PBK, MKI67, and SST were found to be potential drug candidates and significantly correlated with infiltration levels of CD8 + T cells, B cells, macrophages, CD4 + T cells, neutrophils, and dendritic cells. These genes might play a role in sleep disorders via various pathways associated with neurodegeneration and diseases, potentially serving as biomarkers to support treatment and diagnosis.

Smart nanoparticle delivery of cancer vaccines enhances tumor immune responses: a review

Cancer arises from the uncontrolled proliferation of tumor cells within the body. As the incidence of cancer continues to rise, its treatment has become a critical focus for clinicians. The body possesses a tumor immune surveillance mechanism designed to inhibit the proliferation of tumor cells. When tumor-associated mutant antigens appear on the cell surface, antigen-presenting cells, as dendritic cells, present these specific antigens to immune cells, such as T lymphocytes, thereby promoting an immune response and enhancing the cytotoxic effect on tumor cells. Concurrently, the immune system develops immune memory, akin to the response elicited by vaccination. While traditional diseases like tuberculosis and tetanus can be prevented and treated through vaccination, the development of cancer vaccines remains in its nascent stages. Tumor-specific antigens for cancer vaccines can originate from the patient’s own tumor cells or be generated through mutation. Thus, enhancing the presentation of tumor-specific antigens to immune cells is pivotal in anti-tumor immunotherapy. Advances in nanoscience offer novel approaches to tumor immunotherapy. Nanoparticles (NPs) engineered through nanotechnology have garnered significant attention due to their diverse, favorable, and stable properties. These NPs can effectively encapsulate chemotherapy drugs and proteins, facilitating targeted delivery in vivo. Common NPs carriers include liposomes, polymeric nanoparticles, and metal nanoparticles, among others. The development of intelligent NPs delivery systems can enhance efficient antigen presentation, thereby augmenting tumor immune responses. Tumor-specific antigens can be sourced from tumor cells or generated through mutation. In this review, we summarize current methodologies for obtaining various tumor-specific antigens and discuss how these antigens can be delivered to immune cells via different intelligent NPs to bolster anti-tumor immunity. Additionally, from a clinical translation perspective, we explore the challenges and opportunities associated with enhancing tumor immune responses through the smart NP delivery of cancer vaccines. We aim for this review to inspire new strategies in cancer treatment through the use of intelligent NPs and to advance research in cancer vaccines.

Loss of chromosome Y is unrelated to the composition of the tumor microenvironment and patient prognosis in muscle-invasive urothelial bladder cancers

BackgroundLoss of chromosome Y (LOY) has recently been proposed to be associated with cancer aggressiveness, altered T-cell function, and poor prognosis in bladder carcinomas.MethodsChromosome Y was analyzed using fluorescence in-situ hybridization on a tissue microarray containing 2,071 urothelial carcinomas of the urinary bladder from male patients, including 487 patients who had undergone cystectomy for muscle-invasive disease and for whom follow-up data were available. Data on tumor microenvironment were obtained from a previous study.ResultsLOY was found in 26.0% of 1,704 analyzable cancers. In non-invasive cancers, LOY frequency was comparable in pTa G2 (22.8%) and pTa G3 (24.1%, p = 0.8036) carcinomas and slightly increased from pTa to pT2 - 4 carcinomas (23.1% for pTa and 27.2% for pT2 - 4) but these differences were not significant (p = 0.0794). In muscle-invasive cancers, LOY frequency slightly increased from pT2 (25.5%) to pT4 cancers (33.0%), but this association was not significant (p = 0.1814). Among pT2 - 4 cancers, LOY was associated with venous invasion (p = 0.0010) but unrelated to pT, pN, and L-status, as well as to overall, recurrence-free, and cancer-specific survival. Muscle-invasive urothelial carcinomas with and without LOY did not show significant differences in the number of CD8 positive lymphocytes, fraction of CD8 positive intraepithelial lymphocytes, number of macrophages and dendritic cells, and fraction of T helper and T regulatory cells.ConclusionThe lack of a clear association of LOY with histopathological parameters of cancer aggressiveness, patient prognosis, and parameters describing the tumor microenvironment strongly argues against the driving role of LOY in bladder cancer progression and cancer-associated immune reactions.

Immunocytes in the tumor microenvironment: recent updates and interconnections

The tumor microenvironment (TME) is a complex, dynamic ecosystem where tumor cells interact with diverse immune and stromal cell types. This review provides an overview of the TME’s evolving composition, emphasizing its transition from an early pro-inflammatory, immune-promoting state to a later immunosuppressive milieu characterized by metabolic reprogramming and hypoxia. It highlights the dual roles of key immunocytes—including T lymphocytes, natural killer cells, macrophages, dendritic cells, and myeloid-derived suppressor cells—which can either inhibit or support tumor progression based on their phenotypic polarization and local metabolic conditions. The article further elucidates mechanisms of immune cell plasticity, such as the M1/M2 macrophage switch and the balance between effector T cells and regulatory T cells, underscoring their impact on tumor growth and metastasis. Additionally, emerging therapeutic strategies, including checkpoint inhibitors and chimeric antigen receptor (CAR) T and NK cell therapies, as well as approaches targeting metabolic pathways, are discussed as promising avenues to reinvigorate antitumor immunity. By integrating recent molecular insights and clinical advancements, the review underscores the importance of deciphering the interplay between immunocytes and the TME to develop more effective cancer immunotherapies.

In Situ Cancer Vaccines: Redefining Immune Activation in the Tumor Microenvironment.

Cancer is one of the leading causes of mortality worldwide. Nanomedicines have significantly improved life expectancy and survival rates for cancer patients in current standard care. However, recurrence of cancer due to metastasis remains a significant challenge. Vaccines can provide long-term protection and are ideal for preventing bacterial and viral infections. Cancer vaccines, however, have shown limited therapeutic efficacy and raised safety concerns despite extensive research. Cancer vaccines target and stimulate responses against tumor-specific antigens and have demonstrated great potential for cancer treatment in preclinical studies. However, tumor-associated immunosuppression and immune tolerance driven by immunoediting pose significant challenges for vaccine design. In situ vaccination represents an alternative approach to traditional cancer vaccines. This strategy involves the intratumoral administration of immunostimulants to modulate the growth and differentiation of innate immune cells, such as dendritic cells, macrophages, and neutrophils, and restore T-cell activity. Currently approved in situ vaccines, such as T-VEC, have demonstrated clinical promise, while ongoing clinical trials continue to explore novel strategies for broader efficacy. Despite these advancements, failures in vaccine research highlight the need to address tumor-associated immune suppression and immune escape mechanisms. In situ vaccination strategies combine innate and adaptive immune stimulation, leveraging tumor-associated antigens to activate dendritic cells and cross-prime CD8+ T cells. Various vaccine modalities, such as nucleotide-based vaccines (e.g., RNA and DNA vaccines), peptide-based vaccines, and cell-based vaccines (including dendritic, T-cell, and B-cell approaches), show significant potential. Plant-based viral approaches, including cowpea mosaic virus and Newcastle disease virus, further expand the toolkit for in situ vaccination. Therapeutic modalities such as chemotherapy, radiation, photodynamic therapy, photothermal therapy, and Checkpoint blockade inhibitors contribute to enhanced antigen presentation and immune activation. Adjuvants like CpG-ODN and PRR agonists further enhance immune modulation and vaccine efficacy. The advantages of in situ vaccination include patient specificity, personalization, minimized antigen immune escape, and reduced logistical costs. However, significant barriers such as tumor heterogeneity, immune evasion, and logistical challenges remain. This review explores strategies for developing potent cancer vaccines, examines ongoing clinical trials, evaluates immune stimulation methods, and discusses prospects for advancing in situ cancer vaccination.

The Role of TRPA1 as a Prognostic Marker in Colon Adenocarcinoma and its Correlation with Mutations and Immunity

Background: This study aimed to investigate the prognostic value of TRP ion channel genes (TRPICGs) in colorectal adenocarcinoma (COAD) and explore its related mechanisms. Methods: The COAD dataset was downloaded from the Cancer Genome Atlas (TCGA) database. The differential expression genes (DEGs) were screened between COAD and normal samples. The differentially expressed TRPICGs (DE-TRPICGs) were obtained via intersection of DEGs and 28 TRPICGs. The Kaplan-Meier (K-M) survival curve was used to screen DE-TRPICGs with survival differences as prognostic markers. Afterward, the correlation of prognostic marker with clinical, immune cell, copy number variation were explored. Finally, immunohistochemistry (IHC) was used to verify the expression of prognostic marker. Results: Overall, 6003 DEGs were screened, and 6 DE-TRPICGs were obtained. Only TRPA1 was identified as prognostic biomarker. Survival and clinical correlation analyses implied that TRPA1 played an inhibitory role in colon adenocarcinoma pathogenesis and progression. Gene Set Enrichment Analysis (GSEA) indicated that TRPA1 was associated with cell cycle and immune-related pathways. Immune infiltration analysis showed that TRPA1 expression was significantly correlated with the infiltration of B cells, CD4+ T cells, CD8+ T cells, neutrophils and dendritic cells. Eventually, TRPA1 expression was down-regulated at the protein level in COAD samples, which presented consistent results with expression in the database. Conclusion: TRPA1 was identified in COAD as a prognostic marker associated with TRP ion channels, which provided a powerful reference value and a new direction for the diagnosis and treatment of COAD.