Pattern recognition receptors’ and chemokine receptor expression on tonsil dendritic cells

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide and its high mortality rate highlights the necessity of developing novel therapies. Among the different cancer therapy methods, one of the most encouraging ones is dendritic cell (DC)-targeting immunotherapy, where desired antigens are delivered to DCs via antibodies. In this study, we investigated the frequency of CD123+ plasmacytoid DCs, CD1c+ myeloid DCs, CD141+ myeloid DCs and CD141-CD1c- myeloid DCs, in benign and malignant tonsils as well as in malignant nasopharyngeal tissue. We also assessed frequency of the DC subsets expressing CD206, CD207, CLEC9a, DEC205, Dectin-2, TLR-2, TLR-4, XCR1, Dectin-1 and CLECSF14 in benign and malignant tonsils in order to identify candidate receptors as therapeutic targets. Our results showed higher accumulation of DCs in malignant tonsils as compared to benign tonsils. Additionally, an almost 4-fold elevated CD11c myeloid DC/CD123 plasmacytoid DCs ratio was observed in malignant tonsils as compared to the corresponding ratio in benign tonsils. Further, CD123+ plasmacytoid DCs (out of DCs) were found in lower frequency in malignant tonsils as compared to the corresponding subset frequency in benign tonsils, whereas CD141-CD1c- myeloid DCs were more frequent in malignant tonsils compared to benign tonsils. Regarding marker expression on the different subsets, DEC205 and CD207 were expressed by a more considerable proportion of malignant tonsil resident DC subsets in comparison to other pathogen recognition receptors while the frequency of DC subsets expressing CD206, XCR1, Dectin-1 and CLECSF14 was relatively low. CLEC9a, Dectin-2, TLR2 and TLR4 were negligibly expressed. In addition, a significant increase in the frequency of CD1c+CD207+ myeloid DCs compared to CD123+CD207+ plasmacytoid DCs was found in benign tonsils as well as malignant tonsils. Also, the frequency of CD141-CD1c- myeloid DCs expressing XCR1 was higher in malignant tonsils as compared to benign tonsils. Furthermore, although low in frequency, CD141+XCR1+ myeloid DCs were also detected which could be of importance due to these DCs’ excellent ability at cross-presenting tumor antigens. In conclusion, as CD207, DEC205, CD206, Dectin-1, CLECSF14 and XCR1 were shown to be expressed by DC subsets and these receptors are known to be capable of inducing CD4 as well as CD8 T cell responses, we suggest that these receptors, in presence of appropriate costimulatory signals and adjuvants, could be suitable targets for DC-based immunotherapy of malignant tonsils.

Popular Abstract

Immune cells targeting is one of the most promising therapeutic methods against cancer. It involves activation of immune cells so that they are able to fight against tumor cells, and it is performed by directing substances towards surface molecules of the immune cells. In our study, we identified different types of so called dendritic cells, body’s police officers, organizing and regulating the immune system. Additionally, we have identified some surface molecules on these cells (acting like magnets for harmful molecules entering body) in cancer tonsils which could be appropriate molecules for targeting these cells.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide leading to death in 56% of the cases. The tumors occur in head and neck area such as tonsils. In our study, we identified different types of dendritic cells as well as molecules on their surface that can be used as therapeutic targets. The presence of dendritic cells in the tumor tissues supports that dendritic cell therapy is feasible. However, the environment in the tumor tissue can inhibit them from activating the immune system and that is how cancer cells can escape from immune response in tonsils. To avoid this, our study suggests that dendritic cells present in the cancer tonsils could be activated upon targeting their surface molecules and thereby start an effective immune response. Our study thus suggests further studies to fully understand the function of dendritic cells in tumors and how they perform after targeting of different molecules on their surface. Additionally, further studies to find other signals which could boost dendritic cell activation are warranted.

• author: Abolhalaj, Milad
• supervisor: Malin Lindstedt; Kristina Lundberg
• organization: Educational programmes, LTH; Department of Immunotechnology
• alternative title: Flow cytometric analysis of PRRs' and chemokine receptor expression on tonsil resident dendritic cell subsets
• course: KIMM01 20151
• year: 2015
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• keywords: CLEC9a, CD207, CD206, Flow cytometry, pathogen recognition receptors, dendritic cells, Tonsils, immunotherapy, XCR1, CLECSF14, Dectin-1, TLR4, TLR2, Dectin-2, CD205
• language: English
• id: 7864092
• date added to LUP: 2015-09-11 11:06:42
• date last changed: 2015-09-11 11:06:42