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Decreased functional response to Toll like receptor ligands in patients with oral cancer
1Chiplunkar Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India.
Abstract:
Patients with oral cancer (OC) show dysregulation of variety of anti tumor immune responses. To assess the role of Toll like receptor (TLR) signaling in peripheral blood lymphocytes (PBL) from OC patients, we analyzed the expression of TLR2, TLR3, TLR4 and TLR9 on various lymphocyte subsets. Results revealed an increased expression of TLRs on unconventional T cells (like γδ T cells, NKT cells and CD4(+)CD8(+) T cells) as compared to conventional αβ T cells. Functional studies using TLR ligands (CpG, Poly I:C, LPS and Pam3CSK4) showed defects in the TLR mediated signaling in PBLs of OC patients. Proliferation of OC PBLs in response to stimulation with TLR ligands was significantly decreased. TLR ligand induced IFN-γ production by PBLs from OC patients were low as compared to HI. Stimulation with TLR ligands upregulated the levels of activation markers (CD25 and CD69) on PBLs from HI but not from OC patients. TLR ligands CpG, Poly I:C, LPS and Pam3CSK4 significantly augmented the tumor directed cytotoxic response of PBLs from HI but not from OC patients. Our data suggests that impairment of TLR function on PBLs may be another strategy adopted by tumor cells to dampen tumor directed immune responses.
Insights
Toll-like receptor (TLR) signaling is impaired in oral cancer (OC) patients, affecting peripheral blood lymphocytes (PBLs). This dysfunction hinders anti-tumor immunity, suggesting a tumor evasion mechanism.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Oral cancer (OC) is associated with immune response dysregulation.
- Toll-like receptors (TLRs) play a crucial role in immune system activation.
Purpose of the Study:
- To investigate the role of Toll-like receptor (TLR) signaling in peripheral blood lymphocytes (PBLs) of oral cancer patients.
- To analyze TLR expression and function in various lymphocyte subsets from OC patients.
Main Methods:
- Flow cytometry was used to analyze TLR expression on lymphocyte subsets.
- Functional assays assessed TLR-mediated signaling, proliferation, cytokine production (IFN-γ), and activation marker expression (CD25, CD69) upon TLR ligand stimulation.
- Tumor-directed cytotoxic response was evaluated.
Main Results:
- Increased TLR expression was observed on unconventional T cells (γδ T cells, NKT cells, CD4(+)CD8(+) T cells) compared to conventional αβ T cells.
- Peripheral blood lymphocytes (PBLs) from OC patients exhibited impaired TLR signaling, with decreased proliferation and IFN-γ production in response to TLR ligands.
- TLR ligand stimulation failed to upregulate activation markers or enhance tumor-directed cytotoxic responses in OC PBLs, unlike in healthy individuals.
Conclusions:
- Impaired TLR signaling on PBLs in oral cancer patients may represent a mechanism by which tumor cells evade immune surveillance.
- Restoring TLR function could be a potential therapeutic strategy to enhance anti-tumor immunity in oral cancer.
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