RT journal article
T1 KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling
A1 Gimeno, Lourdes
A1 Serrano-López, Emilio M.
A1 Campillo, José A.
A1 Cánovas-Zapata, María A.
A1 Acuña, Omar S.
A1 García Cózar, Francisco José
A1 Martínez-Sánchez, María V.
A1 Martínez-Hernández, María D.
A1 Soto-Ramírez, María F.
A1 López-Cubillana, Pedro
A1 Martínez-Escribano, Jorge
A1 Martínez-García, Jerónimo
A1 Corbalan-García, Senena
A1 Álvarez-López, María R.
A1 Minguela, Alfredo
A2 BiomedicinaBiotecnología y Salud Pública
K1 cancer
K1 CD8+T cells
K1 KIR
K1 immunosurveillance
K1 gene expression
K1 microarray
AB Killer-cell immunoglobulin-like receptors (KIR) are molecules expressed by the most important cells of the immune system for cancer immune vigilance, natural killer (NK) and effector T cells. In this manuscript we study the role that cytotoxic CD8+ T cells expressing KIR receptors could play in cancer immune surveillance. With this objective, frequencies of different KIR+ CD8+ T cell subsets are correlated with the overall survival of patients with melanoma, ovarian and bladder carcinomas. In addition, the gene expression profile of KIR+ CD8+ T cell subsets related to the survival of patients is studied with the aim of discovering new therapeutic targets, so that the outcome of patients with cancer can be improved.Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved.
PB MDPI
SN 2072-6694
YR 2020
FD 2020-10
LK http://hdl.handle.net/10498/24071
UL http://hdl.handle.net/10498/24071
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 15-nov-2026