Document Details

Document Type : Thesis 
Document Title :
THE EFFECT OF TIM-3 EXPRESSION ON DENDRITIC CELLS WITHIN THE TUMOUR MICROENVIRONMENT
تأثير تعبير TIM-3 على الخلايا الجذعية داخل البيئة الدقيقة للورم
 
Subject : Faculty of Science 
Document Language : Arabic 
Abstract : Mature dendritic cells (mDCs) are essential for priming T-cell responses and generating effective anti-tumour immunity. However, producing suppressive factors released within the tumour microenvironment (TME) contributes to tumour escape. As a result, inhibitory molecules may be manipulated on immune cells, including DCs. T cell immunoglobulin and mucin domain-3 (TIM-3) inhibitory receptor is expressed by both tumour and immune cells. The interaction of TIM-3 with galectin-9 (Gal-9) suppresses anti-tumour immunity. Tumour necrosis factor alpha (TNF-α) can induce the expression of TIM-3 on natural killer cells (NKs) in vitro. Therefore, this study aims to explore the effect of the expression of TIM-3 and Gal-9 on DCs. To induce TIM-3 expression, DCs were differentiated from peripheral blood mononuclear cells (PBMCs) of healthy donors by IL-4 and GM-CSF in the presence or absence of lipopolysaccharide (LPS) and TNF-α as well as tumour culture supernatant. DCs have been co-cultured with CD4+ and CD8+ to evaluate the ability of DCs to activate T-cells. The results showed that LPS-treated DCs increased the expression of DC markers (MHC class I & II), maturation markers (CD83), co-stimulatory markers (CD80, CD86) and decreased monocyte markers (CD14). Similar results were observed in TNF-α-treated DCs or in combination with LPS. Interestingly, mDCs lack TIM-3 expression and 90% of immature dendritic cells (iDCs) were TIM-3 positive. No differences in the expression of Gal-9 in TNF-α/LPS-treated cells were found, while it was increased in tumour supernatant-treated DCs. These results revealed that TNF-α and LPS either alone or combined induced the maturation of DCs. Consequently, T-cells lymphocytes were activated in vitro. In addition, the expression of TIM-3 on mDCs was barely detectable in comparison with iDCs. These findings indicate that TNF-α and the supernatant of tumour cells are unable to induce TIM-3 on mDCs but rather increase Gal-9 expression in vitro. Keywords: Dendritic cells (DCs), Mature dendritic cells (mDCs), T cell immunoglobulin and mucin domain-3 (TIM-3), Tumour necrosis factor alpha (TNF-α) and Tumour microenvironment (TME). 
Supervisor : Dr. Fatemah Basingab 
Thesis Type : Master Thesis 
Publishing Year : 1445 AH
2023 AD 
Co-Supervisor : Dr. Alia Aldahlawi 
Added Date : Saturday, November 4, 2023 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
أفنان عبدالغفار القادريAlqadiri, Afnan AbdulqaderResearcherMaster 

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