Dendritic Cells Overcome Cre/Lox Induced Gene Deficiency by Siphoning Material From Neighboring Cells Using Intracellular Monitoring—a Novel Mechanism of Antigen Acquisition DOI Creative Commons

Christopher H. Herbst,

Aurélie Bouteau,

Evelin J. Menykő

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 25, 2023

Macrophages and dendritic cells (DCs) in peripheral tissue interact closely with their local microenvironment by scavenging protein nucleic acids released neighboring cells. Material transfer between cell types is necessary for pathogen detection antigen presentation, but thought to be relatively limited scale. Recent reports, however, demonstrate that the quantity of transferred material can quite large when DCs are direct contact live This observation may problematic conditional gene deletion models assume products will remain they produced in. Here, we investigate whether deletions induced widely used Cre/Lox system overcome at level DCs. Of concern, using human Langerin Cre mouse model, find epidermal Langerhans CD11b+CD103+ mesenteric if deleted expressed Surprisingly, also mechanism does not resemble known mechanisms uptake, dependent on extra- intracellular calcium, PI3K, scavenger receptors, mediates a majority We term this novel process

Language: Английский

Cross-priming in cancer immunology and immunotherapy DOI
Carlos Luri‐Rey, Álvaro Teijeira, Stefanie K. Wculek

et al.

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Language: Английский

Citations

2
Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management DOI Open Access

Melika Loriamini,

Christine Cserti‐Gazdewich, Donald R. Branch

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4296 - 4296

Published: April 12, 2024

Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one's own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association diseases infections). There several different categories AIHAs recognized according to their features in direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing portion band 3 (wherein DAT may positive IgG, C3d both). Treatment involves glucocorticoids and steroid-sparing agents consider IVIG monoclonal CD20, CD38 C1q. (2) Cold-antibody due IgMs range from cold agglutinin syndrome (CAS) agglutin disease (CAD). typically specific Ii group system, former being polyclonal latter (CAD) more severe entity. The either case is only C3d. Foundationally, patient kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on options C1q C5. (3) Mixed AIHA, also called combined warm has both C3d, approaches inclusive those appropriate wAIHA AIHA. (4) Paroxysmal hemoglobinuria (PCH), termed Donath-Landsteiner test-positive driven upstream by biphasic cold-reactive antibody recruiting complement. Although usually self-remitting, management (5) Direct test-negative (DAT-neg AIHA), below detection thresholds DAT, non-detected IgM IgA antibodies, managed as wAIHA. (6) Drug-induced immune anemia (DIIHA) appears and/or Some cases resolve after ceasing instigating drug. (7) Passenger lymphocyte syndrome, found transplantation, caused B-cells transferred an antigen-negative donor whose react recipient who produces antigen-positive RBCs. This comprehensive review will discuss detail each these provide information diagnosis, pathophysiology modalities.

Language: Английский

Citations

10
Antigen escape in CAR-T cell therapy: Mechanisms and overcoming strategies DOI Open Access
Haolong Lin,

Xiuxiu Yang,

Shanwei Ye

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117252 - 117252

Published: Aug. 3, 2024

Chimeric antigen receptor T (CAR-T) cell therapy has shown promise in treating hematological malignancies and certain solid tumors. However, its efficacy is often hindered by negative relapses resulting from escape. This review firstly elucidates the mechanisms underlying escape during CAR-T therapy, including enrichment of pre-existing target-negative tumor clones, gene mutations or alternative splicing, deficits processing, redistribution, lineage switch, epitope masking, trogocytosis-mediated loss. Furthermore, we summarize various strategies to overcome escape, evaluate their advantages limitations, propose future research directions. Thus, aim provide valuable insights enhance effectiveness therapy.

Language: Английский

Citations

8
Recent Findings on Therapeutic Cancer Vaccines: An Updated Review DOI Creative Commons
Sara Sheikhlary, David Humberto Lopez,

Sophia Moghimi

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 503 - 503

Published: April 21, 2024

Cancer remains one of the global leading causes death and various vaccines have been developed over years against it, including cell-based, nucleic acid-based, viral-based cancer vaccines. Although many effective in vivo clinical studies some FDA-approved, there are major limitations to overcome: (1) developing universal vaccine for a specific is difficult, as tumors with different antigens individuals, (2) tumor may be similar body’s own antigens, (3) possibility recurrence. Therefore, personalized ability distinguish between indispensable. This paper provides comprehensive review types highlights important factors necessary efficient Moreover, application other technologies therapy discussed. Finally, several insights conclusions presented, such using cold plasma stem cells future vaccines, tackle developmental process.

Language: Английский

Citations

7
Antigen cross-presentation by dendritic cells: A critical axis in cancer immunotherapy DOI
Christine Moussion, Lélia Delamarre

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 71, P. 101848 - 101848

Published: Nov. 29, 2023

Language: Английский

Citations

15
Merocytophagy is an integrin-stabilized macrophage response to microbes reliant on Syk signaling DOI Creative Commons
Kelly N. Deobald, Shaun Steele, Sedelia R. Dominguez

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Macrophages and dendritic cells acquire bacteria cytosolic content from other without killing the donor cell through a trogocytosis-associated process termed merocytophagy. While characteristics of this behavior have been partially identified, mechanism potential contribution to response infection are unclear. Here, we reveal that wide range distinct species stimulate enhanced merocytophagy in macrophages pattern recognition receptor (PRR). Further, found cell-to-cell transfer Francisella tularensis occurs predominantly MyD88-independent manner, relying on spleen tyrosine kinase (Syk) activity. Syk signaling during also results increased surface expression adhesion proteins integrin α4, β1, ICAM-1 CD44 at site transfer, depleting these molecules impairs merocytophagic transfer. Altogether, our data demonstrate is host facilitated by tight binding which molecularly resembles an immunological synapse between macrophages.

Language: Английский

Citations

0
Autoimmune Hemolytic Anemias DOI Open Access

Melika Loriamini,

Christine Cserti‐Gazdewich, Donald R. Branch

et al.

Published: March 13, 2024

Autoimmune hemolytic anemias (AIHAs) are conditions whereby a person produces an antibody to their own red blood cells (RBCs). These can be primary with unknown cause or secondary, associated diseases infections. There seven different categories of AIHA, warm-antibody AIHA (wAIHA); cold-antibody that includes cold agglutinin syndrome (CAS) and agglutin disease (CAD); mixed also called combined warm AIHA; paroxysmal hemoglobinuria (PCH) termed Donath-Lansteiner test-positive direct antiglobulin test-negative (DAT-neg AIHA); drug-induced immune anemia (DIIHA); passenger lymphocyte syndrome. This review will discuss each these AIHAs provide information on diagnosis treatment.

Language: Английский

Citations

2
Primary Amoebic Meningoencephalitis Caused by Naegleria fowleri DOI
Ediane Gallo

International Healthcare Review (online), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

BACKGROUND: Naegleria fowleri is a free-living amoeba (FLA) ubiquitous to the environment. Although harmless when ingested, it can access person's brain through nasal cavities and cause an acute infection known as primary amoebic meningoencephalitis (PAM). METHODS: A scoping literature review presenting valuable information healthcare providers about critical features pathogenesis of N. by synthesizing existing databases accessible on National Library Medicine (NCBI) platform. RESULTS: The prodromal stage PAM vague often misdiagnosed viral or bacterial meningitis, regardless treatments supportive care, patients rapidly succumb once symptoms appear. Delayed ineffective along with unnecessary tests procedures, irreversible damage ultimately lead death. Additionally, exact mechanism action for treatment remains unclear, standard therapeutic protocol recommended Centers Disease Control Prevention (CDC) consists aggressive but unreliable combination antibiotics. CONTRIBUTION TO EVIDENCE-BASED CARE: rare disease high fatality rate, so prioritizing prevention early detection highlights importance preparedness in settings. postmortem tissue examination typically required confirm diagnosis. Overall, raising awareness risks prompt diagnosis crucial reducing incidence impact this deadly disease.

Language: Английский

Citations

2
Antigen presentation for central tolerance induction DOI
Ludger Klein, Elisabetta Petrozziello

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Language: Английский

Citations

2
Trogocytosis in CAR immune cell therapy: a key mechanism of tumor immune escape DOI Creative Commons

Yizhao Chen,

Qianling Xin,

Mengjuan Zhu

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 28, 2024

Immune cell therapy based on chimeric antigen receptor (CAR) technology platform has been greatly developed. The types of CAR immune have expanded from T cells to innate such as NK and macrophages, the diseases treated hematological malignancies non-tumor fields infectious autoimmune diseases. Among them, CAR-T CAR-NK observed examples rapid remission in approved clinical trials, but efficacy is unstable plagued by tumor resistance. Trogocytosis a special phenomenon intercellular molecular transfer that common system achieved recipient through acquisition internalization donor cell-derived molecules mediates effects. Recently, novel short-term drug resistance mechanism trogocytosis proposed, bidirectional exchange between triggered partially explains long-term relapse after treatment with cells. In this review, we summarize research progress immunotherapy, discuss influencing factors its direct indirect interference emphasize can further release potential therapy.

Language: Английский

Citations

2