Gimeno Lourdes, Serrano-López Emilio M, Campillo José A, Cánovas-Zapata María A, Acuña Omar S, García-Cózar Francisco, Martínez-Sánchez María V, Martínez-Hernández María D, Soto-Ramírez María F, López-Cubillana Pedro, Martínez-Escribano Jorge, Martínez-García Jerónimo, Corbalan-García Senena, Álvarez-López María R, Minguela Alfredo
Immunology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), 30120 Murcia, Spain.
Human Anatomy Department, University of Murcia (UM), 30100 Murcia, Spain.
Cancers (Basel). 2020 Oct 15;12(10):2991. doi: 10.3390/cancers12102991.
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.
杀伤细胞免疫球蛋白样受体（KIR）由自然杀伤（NK）细胞和效应T细胞表达。尽管KIR⁺ T细胞在肿瘤患者中会积累，但其在癌症免疫反应中的作用仍不清楚。本研究通过分析249例患者（80例黑色素瘤、80例膀胱癌和89例卵巢癌）血液中诊断时KIR⁺CD8⁺ T细胞的频率、它们与患者总生存期（OS）的关系以及它们的基因表达谱，探讨了KIR⁺CD8⁺ T细胞在癌症免疫监视中的作用。在存活患者中，KIR2DL1⁺ CD8⁺ T细胞在HLA - C2配体存在的情况下会扩增，但在死亡患者中则不会。相反，HLA - C1配体的存在与KIR2DL2/S2⁺ CD8⁺ T细胞的剂量依赖性扩增以及较短的OS相关。KIR与其特异性配体的相互作用深刻影响了CD8⁺ T细胞的表达谱，涉及多个信号通路、效应功能、分泌组，进而影响细胞微环境，这可能会影响它们的癌症免疫监视能力。KIR2DL1/S1⁺ CD8⁺ T细胞显示出与高效肿瘤免疫监视相关的基因表达特征，而KIR2DL2/L3/S2⁺CD8⁺ T细胞显示出与抑制性抗肿瘤反应相关的转录组特征。这些结果可能为发现新的治疗靶点奠定基础，从而改善癌症患者的预后。
