CD4+ T cell memory

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(6), P. 903 - 914

Published: May 8, 2023

Language: Английский

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T Cells in Colorectal Cancer: Unravelling the Function of Different T Cell Subsets in the Tumor Microenvironment

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11673 - 11673

Published: July 19, 2023

Therapeutic options for metastatic colorectal cancer (mCRC) are very limited, and the prognosis using combination therapy with a chemotherapeutic drug targeted agent, e.g., epidermal growth factor receptor or tyrosine kinase, remains poor. Therefore, mCRC is associated poor median overall survival (mOS) of only 25–30 months. Current immunotherapies checkpoint inhibitor blockade (ICB) have led to substantial change in treatment several cancers, such as melanoma non-small cell lung cancer. In CRC, ICB has limited effects, except patients microsatellite instability-high (MSI-H) mismatch repair-deficient (dMMR) tumors, which comprise about 15% sporadic CRC 4% CRC. The vast majority CRCs microsatellite-stable (MSS) tumors low levels infiltrating immune cells, immunotherapy no clinical benefit so far. Immunotherapy inhibitors requires presence T cells into tumor microenvironment (TME). This makes most important effector TME, evidenced by establishment immunoscore—a method estimate patients. contains types that anti-tumorigenic, CD8+ pro-tumorigenic, regulatory (Tregs) helper 17 (Th17) cells. However, even show marked heterogeneity, they can become exhausted, enter state hyporesponsiveness dysfunctional express high molecules, targets ICB. To kill need recognition MHC class I, often downregulated on this case, population unconventional γδ overcome limitations conventional an αβT receptor. recognize antigens MHC-independent manner, thus acting bridge between innate adaptive immunity. Here, we discuss effects different subsets special emphasis possibility them CAR-T therapy. We explain exclusion possibilities enable these “cold” tumors.

Language: Английский

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The multiple roles of interferon regulatory factor family in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 9, 2024

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores diverse functions nine mammalian IRF members, each featuring conserved domains essential for interactions with other factors cofactors. These allow IRFs to modulate broad spectrum processes, encompassing host defense, response, cell development. Conversely, their pivotal role in regulation implicates them pathophysiology various diseases, such as infectious autoimmune disorders, metabolic cancers. In this context, display dichotomous nature, functioning tumor suppressors promoters, contingent upon specific disease milieu. Post-translational modifications IRFs, including phosphorylation ubiquitination, play crucial modulating function, stability, activation. As prospective biomarkers therapeutic targets, present promising opportunities intervention. Further research is needed elucidate precise mechanisms governing regulation, potentially pioneering innovative strategies, particularly cancer treatment, where equilibrium activities paramount importance.

Language: Английский

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CD4+ T cells in antitumor immunity

Trends in cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Unraveling the complex interplay between anti-tumor immune response and autoimmunity mediated by B cells and autoantibodies in the era of anti-checkpoint monoclonal antibody therapies

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 22, 2024

The intricate relationship between anti-tumor immunity and autoimmunity is a complex yet crucial aspect of cancer biology. Tumor microenvironment often exhibits autoimmune features, phenomenon that involves natural the induction humoral responses against self-antigens during tumorigenesis. This facilitated by orchestration immunity, particularly within organized structures like tertiary lymphoid (TLS). Paradoxically, significant number patients do not manifest features course their illness, with rare instances paraneoplastic syndromes. discrepancy can be attributed to various immune-mediated locks, including regulatory or suppressive immune cells, anergic autoreactive lymphocytes, effector cells exhaustion due chronic stimulation. Overcoming these locks holds risk induce mechanisms progression, notably observed anti-immune checkpoint therapies, in contrast more conventional treatments chemotherapy radiotherapy. Therefore, challenge arises managing immune-related adverse events (irAEs) induced inhibitors treatment, as decoupling them from activity poses clinical dilemma. review summarizes recent advances understanding link B-cell driven reactions patients, discusses implications this relationship.

Language: Английский

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T Follicular Helper Cell Heterogeneity

Annual Review of Immunology, Journal Year: 2023, Volume and Issue: 42(1), P. 127 - 152

Published: Dec. 7, 2023

T follicular helper (Tfh) cells specialize in helping B and are therefore critical contributors to the generation of humoral immunity. Tfh aid immunoglobulin class-switch recombination support germinal center response, thereby promoting affinity maturation immune memory. Although their primary function is promote cell responses, also display phenotypic functional diversity determined by immunological spatial contexts from which they emerge. We review recent advances understanding heterogeneity within subsets along with differentiation migratory trajectory, phenotypes adopt, ontological relationships one another, respective environments.

Language: Английский

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Nanoengineering Calcium Peroxide‐Based Site‐Specific Delivery Platform to Efficiently Activate the cGAS‐STING Pathway for Cancer Immunotherapy by Amplified Endoplasmic Reticulum Stress

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(18)

Published: Jan. 23, 2024

Abstract Currently, the understanding of cyclic GMP‐AMP synthase (cGAS)‐stimulator interferon genes (STING) pathway's involvement in efficient immunotherapy mainly revolves around role mitochondria or nucleus modulation. Nonetheless, endoplasmic reticulum (ER) stress activating cGAS‐STING mechanism to boost immunity against tumors remains essentially unexplored. Herein, novel findings demonstrating that ER can be used as a strategy for stimulating pathway, thereby augmenting immune response cancer, are presented. To accomplish this objective, ER‐targeting p ‐methylbenzene sulfonamide‐tailored IR780 (p‐780) is synthesized and it loaded into CaO 2 nanoparticles, which further functionalized with distearoyl phosphoethanolamine‐polyethylene glycol（DSPE‐PEG）‐biotin form PEG/CaO @p‐780 NPs. The disruption calcium homeostasis, coupled heightened levels reactive oxygen species (ROS) mediated by p‐780, along hyperpyrexia, collectively contributes amplification stress. This cascade events effectively triggers pathway and, parallel, facilitates degradation programmed cell death 1 ligand (PD‐L1) protein. In addition, released through decomposition expected promote p‐780–mediated phototherapy, while reversing immunosuppressive tumor microenvironment associated hypoxia. Furthermore, DSPE‐PEG‐biotin site‐specific drug delivery active targeting biotin receptor. Collectively, nanoparticles successfully activate systemic antitumor enhancing

Language: Английский

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Comprehensive analysis of FOXM1 immune infiltrates, m6a, glycolysis and ceRNA network in human hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 10, 2023

Background Forkhead box M1 (FOXM1) is a member of the (Fox) transcription factor family. It regulates cell mitosis, proliferation, and genome stability. However, relationship between expression FOXM1 levels m6a modification, immune infiltration, glycolysis, ketone body metabolism in HCC has yet to be fully elucidated. Methods Transcriptome somatic mutation profiles were downloaded from TCGA database. Somatic mutations analyzed by maftools R package visualized oncoplots. GO, KEGG GSEA function enrichment was performed on co-expression using R. We used Cox regression machine learning algorithms (CIBERSORT, LASSO, random forest, SVM-RFE) study prognostic value infiltrating characteristic cells HCC. The m6A RNA-seq CHIP-seq. competing endogenous RNA (ceRNA) network construction relies multiMiR package, ENCORI, miRNET platforms. Results highly expressed associated with poorer prognosis. At same time, level significantly related T, N, stage. Subsequently, based strategies, we found that infiltration T follicular helper (Tfh) risk affecting prognosis patients. high Tfh poor overall survival rate Besides, CHIP-seq demonstrated modification binding promoter IGF2BP3 affects glycolytic process initiating HK2 PKM A ceRNA successfully obtained, including - has-miR-125-5p – DANCR/MIR4435-2HG Conclusion Our implicates aberrant crucial for genes glycolysis at transcriptional level. Furthermore, specific can as potential therapeutic target

Language: Английский

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Dual Functions of T Lymphocytes in Breast Carcinoma: From Immune Protection to Orchestrating Tumor Progression and Metastasis

Cancers, Journal Year: 2023, Volume and Issue: 15(19), P. 4771 - 4771

Published: Sept. 28, 2023

Breast cancer (BC) is the most common type in women and second leading cause of death. Despite recent advances, mortality rate BC still high, highlighting a need to develop new treatment strategies including modulation immune system immunotherapies. In this regard, understanding complex function involved cells their crosstalk with tumor great importance. T-cells are recognized as important microenvironment divided into several subtypes helper, cytotoxic, regulatory according transcription factors, markers, functions. This article attempts provide comprehensive review role T-cell subsets prognosis patients BC, between T-cells. The literature overwhelmingly contains controversial findings mainly due plasticity within inflammatory conditions use different panels for phenotyping. However, investigating immunity depends on variety factors types or subtypes, stage disease, localization tissue presence cytokines.

Language: Английский

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CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer

Cancer Research, Journal Year: 2023, Volume and Issue: 83(18), P. 3026 - 3044

Published: June 28, 2023

Abstract Regulatory T cells (Treg) impede effective antitumor immunity. However, the role of Tregs in clinical outcomes patients with triple-negative breast cancer (TNBC) remains controversial. Here, we found that an immunosuppressive TNBC microenvironment is marked by imbalance between effector αβCD8+ and harboring hallmarks highly suppressive (eTreg). Intratumoral eTregs strongly expressed PD-1 persisted resistant to blockade. Importantly, CD25 was most selective surface marker primary metastases compared other candidate targets for eTreg depletion currently being evaluated trials advanced TNBC. In a syngeneic model, use Fc-optimized, IL2 sparing, anti-CD25 antibodies synergized blockade promote systemic immunity durable tumor growth control increasing T-cell/Treg ratios tumors periphery. Together, this study provides rationale translation therapy improve responses Significance: An CD8+ CD25high marks microenvironments αPD-1–resistant can be reversed through Treg increase αPD-1 efficacy.

Language: Английский

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