title: Decreased functional response to Toll like receptor ligands in patients with oral cancer.
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.
authors.affiliation: Chiplunkar Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India.
authors.forename: B
authors.initials: B
authors.lastname: Paleja
authors.forename: A
authors.initials: A
authors.lastname: Anand
authors.forename: D
authors.initials: D
authors.lastname: Chaukar
authors.forename: A
authors.initials: A
authors.lastname: D'Cruz
authors.forename: S
authors.initials: S
authors.lastname: Chiplunkar
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009062:Mouth Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008024:Ligands; D051193:Toll-Like Receptors; D011070:Poly I-C
keywords: CpG ODN; CpG oligodeoxynucleotide Type A; IDO; LPS; PGE2; PIC/Poly I:C; Pam3; Pam3CSK4; indole 2,3-dioxygenase; lipopolysaccharide; polyinosinic:polycytidylic acid; prostaglandin E2