Sustained Antigen Stimulation to Evoke and Study Negative feedback Systems responsible for Self-Tolerance/Tumor Immune Escape and transition to the M2 macrophage

Published: April 18, 2025

Abstract Chronic inflammation plays an obscure role in cancer initiation, with broad references implicating immune exhaustion (IEX) or free radical mediated cell damage. is, however, paradoxically synonymous the term “immune tolerance” which other cases presents itself as a therapeutic limitation to efficacy of tumor therapies particularly those involving microbial -associated molecular patterns (MAMPs) regimens. As “tolerance” remains this day “phenomenon” there is pressing need fully understand every biological aspect apparent negative feedback response, because doing so will serve guide development targeted therapies. In work, we employ rudimentary model, can be adopted it possible provoke through sustained antigen stimulation immunocompetent cells, monitor, define and characterize phenotype evolution using next generation whole transcriptome sequencing + validation studies. This model used study /create vitro “M2” phenotype, involved aggressive tumors synergistic rapid expansion myeloid-derived suppressor cells (MDSCs), dysfunctional CD8+ T cytotoxic (CTL)/ natural killer (NK) cells. Briefly, data shows dominates at 7 11 days, after acute being associated phase specific (time dependent) elevated checkpoints; e.g. PDL1+/MSN, HAVCR2/TIM-3+, SPP1+, C3ar1+, CD73+, IL1RN+, LILRbs+, glycoproteins, integrins etc. Here report on bidirectional changes aligning escape, much centered around loss host defense against viral infection malignancy. Negative rampant induction degradative proteases, SOCS/JAK/STAT/IL-10, CCL2/7 axis tantamount MHC1/2 recognition systems, Type I interferon NOD signaling, antiviral/antibacterial defense, p62/SQSTM also disturbed metabolic signature. The work demonstrates that colloquial terms “tolerance IEX” are somewhat flawed terminology, potent, intentional formidable offense eradicate active arm defense. Truncated /Removed due word count show aligns six distinct chronological differential gene (DEG) expression circumscribe extensive suppression dominate during chronic inflammation. These involve following time dependent patterns: 1) transcripts overexpressed, checkpoint receptors; etc.; 2) overexpressed only chronic; e.g cytokine signaling (SOC3/Jak/Stat), cyto/chemokines (IL-10, CCL2, CCL7), proteases (cathepsins L, D, K, Adam 8, PIM2), adhesives (TSPAN3, QSOX1, PDPN, ITGA5), (PLK2, ADGRE1, CALM1, PCNA, etc.); 3) downregulated severe collective MHC1/II presentation capacity (CD74, H2-Q4, H2-Q6, etc.), (IFN) type systems; 4) only, including OXPHOS/metabolic genes (Aldo A, C, Eno2, Gpi1, (Lyz1, Lyz2, Card19, Ninj1), autophagy-related (p62/SQSTM1). category Tolerance were: 5) induced sharply acute, no longer responsive IFN 1 antiviral response (OAS, BST2, ISG15, ISG20, IRF7, RSAD2/Viperin), TLR2, antibacterial (SAA3, SP140), proinflammatory cytokines (CCL5, TNF, IL1a, IL1b) along IL-1/TLR axis. Last, 6) reverse tolerance, corresponded restored baseline levels maintain mitotic thymosin homeostasis. conclusion, these suggest precipitates feedback, same targets sought today

Language: Английский

---

Colocalization of cancer-associated biomarkers on single extracellular vesicles for early detection of cancer

Journal of Molecular Diagnostics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

---

Bone Marrow Stromal Cell Antigen 2 is Broadly Expressed in the Different Pluripotent States of Human Pluripotent Stem Cells and is Required for the Maintenance of Pluripotency Genes

Published: Jan. 1, 2024

Language: Английский

---

APOE Protects Against Severe Infection with Mycobacterium tuberculosis by Restraining Production of Neutrophil Extracellular Traps

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

While neutrophils are the predominant cell type in lungs of humans with active tuberculosis (TB), they relatively scarce most strains mice that used to study disease. However, similar humans, account for approximately 45% CD45+ cells

Language: Английский

---

Bone marrow stromal cell antigen 2 is broadly expressed in the different pluripotent states of human pluripotent stem cells and regulates the expression of pluripotency genes and three germ layer markers

Human Cell, Journal Year: 2024, Volume and Issue: 38(1)

Published: Dec. 24, 2024

Language: Английский

---

Effect of cryoablation on the spatial transcriptomic landscape of the immune microenvironment in non-small cell lung cancer

Journal of Cancer Research and Therapeutics, Journal Year: 2024, Volume and Issue: 20(7), P. 2141 - 2147

Published: Dec. 1, 2024

Language: Английский

---