CD8+ T lymphocytes isolated from renal cancer patients recognize tumour cells through an HLA- and TCR/CD3-independent pathway

Lionello, Ilaria; Mangia, Patrizia; Gattinoni, Luca; Pende, Daniela; Cippone, Arcadi; Sensi, Marialuisa; Rigatti, Patrìzio; Traversari, Catia

doi:10.1007/s00262-006-0268-x

Cited by 4 publications

(4 citation statements)

References 32 publications

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“…For all we know, at the molecular level, the tumor often involves various cells of the immune-system participation, and it is a complex interplay that has many stages and steps related to the tumor microenvironment. The role of regulatory T cells in cancer has gained concern, and regulatory T cells play a vital role in the progression of KIRC in internal and peripheral tissues (52)(53)(54). The high percentages of regulatory T cell activation in peripheral blood or tumorous tissues were correlated to low survival rates in kidney cancer (55)(56)(57).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Radiomic Nomogram for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma

et al. 2021

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PurposeThe present study aims to comprehensively investigate the prognostic value of a radiomic nomogram that integrates contrast-enhanced computed tomography (CECT) radiomic signature and clinicopathological parameters in kidney renal clear cell carcinoma (KIRC).MethodsA total of 136 and 78 KIRC patients from the training and validation cohorts were included in the retrospective study. The intraclass correlation coefficient (ICC) was used to assess reproducibility of radiomic feature extraction. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) as well as multivariate Cox analysis were utilized to construct radiomic signature and clinical signature in the training cohort. A prognostic nomogram was established containing a radiomic signature and clinicopathological parameters by using a multivariate Cox analysis. The predictive ability of the nomogram [relative operating characteristic curve (ROC), concordance index (C-index), Hosmer–Lemeshow test, and calibration curve] was evaluated in the training cohort and validated in the validation cohort. Patients were split into high- and low-risk groups, and the Kaplan–Meier (KM) method was conducted to identify the forecasting ability of the established models. In addition, genes related with the radiomic risk score were determined by weighted correlation network analysis (WGCNA) and were used to conduct functional analysis.ResultsA total of 2,944 radiomic features were acquired from the tumor volumes of interest (VOIs) of CECT images. The radiomic signature, including ten selected features, and the clinical signature, including three selected clinical variables, showed good performance in the training and validation cohorts [area under the curve (AUC), 0.897 and 0.712 for the radiomic signature; 0.827 and 0.822 for the clinical signature, respectively]. The radiomic prognostic nomogram showed favorable performance and calibration in the training cohort (AUC, 0.896, C-index, 0.846), which was verified in the validation cohort (AUC, 0.768). KM curves indicated that the progression-free interval (PFI) time was dramatically shorter in the high-risk group than in the low-risk group. The functional analysis indicated that radiomic signature was significantly associated with T cell activation.ConclusionsThe nomogram combined with CECT radiomic and clinicopathological signatures exhibits excellent power in predicting the PFI of KIRC patients, which may aid in clinical management and prognostic evaluation of cancer patients.

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Section: Discussionmentioning

confidence: 99%

Development and Validation of a Radiomic Nomogram for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma

et al. 2021

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“…Human lung cancer (MR300 and MR232 [62], human melanoma (MSR3, and GR4-mel) [63], and pro-monocytic human myeloid leukaemia (U937) cells were cultured in RPMI medium (Lonza, Basel, CH, USA) supplemented with 10% fetal bovine serum (FBS, heat inactivated; HyClone, Logan, UT, USA), 2 mM glutamine, 100 units/mL penicillin and streptomycin (Gibco, Gaithersburg, MD, USA). Human umbilical vein endothelial cells (HUVECs; Promocell, Heidelberg, DE, USA) were grown in complete EGM-2 (Lonza).…”

Section: Methodsmentioning

confidence: 99%

Mechanism of Action of the Tumor Vessel Targeting Agent NGR-hTNF: Role of Both NGR Peptide and hTNF in Cell Binding and Signaling

Valentinis

Porcellini

Asperti

et al. 2019

IJMS

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NGR-hTNF is a therapeutic agent for a solid tumor that specifically targets angiogenic tumor blood vessels, through the NGR motif. Its activity has been assessed in several clinical studies encompassing tumors of different histological types. The drug’s activity is based on an improved permeabilization of newly formed tumor vasculature, which favors intratumor penetration of chemotherapeutic agents and leukocyte trafficking. This work investigated the binding and the signaling properties of the NGR-hTNF, to elucidate its mechanism of action. The crystal structure of NGR-hTNF and modeling of its interaction with TNFR suggested that the NGR region is available for binding to a specific receptor. Using 2D TR-NOESY experiments, this study confirmed that the NGR-peptides binds to a specific CD13 isoform, whose expression is restricted to tumor vasculature cells, and to some tumor cell lines. The interaction between hTNF or NGR-hTNF with immobilized TNFRs showed similar kinetic parameters, whereas the competition experiments performed on the cells expressing both TNFR and CD13 showed that NGR-hTNF had a higher binding affinity than hTNF. The analysis of the NGR-hTNF-triggered signal transduction events showed a specific impairment in the activation of pro-survival pathways (Ras, Erk and Akt), compared to hTNF. Since a signaling pattern identical to NGR-hTNF was obtained with hTNF and NGR-sequence given as distinct molecules, the inhibition observed on the survival pathways was presumably due to a direct effect of the NGR-CD13 engagement on the TNFR signaling pathway. The reduced activation of the pro survival pathways induced by NGR-hTNF correlated with the increased caspases activation and reduced cell survival. This study demonstrates that the binding of the NGR-motif to CD13 determines not only the homing of NGR-hTNF to tumor vessels, but also the increase in its antiangiogenic activity.

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“…Engagement of T cell receptor (TCR) by peptide-MHC complexes without co-stimulatory molecules results in profoundly anergic T cells that are unable to respond to further activation. 8,[21][22][23][24][25][26][27][28][29][30][31][32] It is therefore necessary to evaluate the expression pattern of these immune related molecules in tumor cell for further understanding the mechanism of tumor immune evasion and tumor development, and for identification of immunotherapeutic targets.…”

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confidence: 99%

Expression of immune-related molecules in primary EBV positive chinese nasopharyngeal carcinoma: Associated with latent membrane protein 1 (LMP1) expression

Li¹,

Zhang²,

Xie³

et al. 2007

Cancer Biology & Therapy

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To understand the role of Epstein-Barr virus (EBV) and viral products in associated with immunophenotype and clinical outcome of primary nasopharyngeal carcinoma (NPC), the expression levels of chemokines IFN-g-induced protein 10 (IP-10, CXCL10), stromal-derived factor-1 (SDF-1, CXCL12) and its receptor CXCR4 was investigated in 56 primary NPC biopsy specimens from Chinese NPC patients in parallels with LMP1 antigen and EBER1 by immunohistochemisty (IHC) and in situ hybridization (ISH). Moreover, the expression levels of HLA class I (b-microglobulin) and II antigen (HLA-DR), and co-stimulatory molecule CD54 were also evaluated in 31 out of these 56 patients using immunohistochemisty (IHC). Our results showed that (a) the elevated expression levels of IP10, SDF-1, CXCR4, b-microglobulin, HLA-DR and CD54 in NPC lesions was 66%, 36%, 30%, 42%, 55% and 69%, respectively. The differentiated nonkeratinizing and undifferentiated types of nasopharyngeal carcinoma (NPC) are associated with Epstein-Barr virus (EBV) in South China, which has the highest incidence rate in the world. 1 The EBV latent type II antigens include nuclear antigen 1 (EBNA1), and latent membrane protein 1 (LMP1, in approximately 50%, seen in ref.2) and protein 2 (LMP2), in addition small non-polyadenylated viral RNAs non-coding nuclear RNAs (EBERs) and BamHI-A rightward transcripts (BARTs) expressed in NPC tumor cells. The expressions of EBV antigens in NPC tumor cells provide the targets for adoptive immunotherapy. [3][4][5][6] However, the poorly differentiated NPC is always characterized by the presence of a highly cellular lymphoid stroma admixed with tumor cells. 7 However, the role of local immunity surrounding NPC cells and the role EBV and viral products expressed in tumor cell remain unclear, which is associated with the expression of immune-related molecules including chemokines and receptors, HLA class I and II antigens, and co-stimulatory molecules and the role of EBV and viral products to alter the expression of immune-related molecules on tumor cells. It has been reported that the expression pattern of immune related-molecules on tumor cells will affect the outcome of T-cell-based adoptive immunotherapy for NPC. [8][9][10] In the tumor bed, chemokines and cytokines are secreted by both tumor-infiltrating immune cells and the tumor cells, and these chemokines and cytokines are capable of pleiotropic effects. 8 For example, IP-10 is a CXC chemokine produced by endothelial cells and macrophages post-stimulated by IFNg. IP-10 can induce rapid and transient adhesion of human IL-2-stimulated T lymphocytes to endothelial cells through its receptor CXCR3, which is selectively expressed on activated T cells. It is thought that expression of IP-10 in tumor cells induces potent anti-tumor functions, such as induction of the Th1 immune response and inhibition of angiogenesis. 11-13 SDF-1 is a a-chemokine, and bind to the only receptor CXCR4. Recent studies suggested that the SDF-1/CXCR4 axis play an important and unique role not only in th...

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CD8+ T lymphocytes isolated from renal cancer patients recognize tumour cells through an HLA- and TCR/CD3-independent pathway

Cited by 4 publications

References 32 publications

Development and Validation of a Radiomic Nomogram for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma

Development and Validation of a Radiomic Nomogram for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma

Mechanism of Action of the Tumor Vessel Targeting Agent NGR-hTNF: Role of Both NGR Peptide and hTNF in Cell Binding and Signaling

Expression of immune-related molecules in primary EBV positive chinese nasopharyngeal carcinoma: Associated with latent membrane protein 1 (LMP1) expression

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