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Nadia Guerra

Publications and source records attributed to Nadia Guerra.

5 recordsLinked to original sources
PubMed2004

Analysis of the natural killer mediated immune response in metastatic renal cell carcinoma patients.

Metastatic renal cell carcinomas (MRCC) are considered as immunogeneic tumors on the basis of the clinical responses observed in patients treated by IL-2. However, renal cell carcinoma patients are also characterized by alterations of the immune response that may compromise the immunotherapeutic approaches. In our study, we have studied the phenotype and the functional capacities of peripheral NK cells in a panel of neprectomized metastatic renal cell carcinoma patients. NK cells were harvested by negative immunoselection from fresh peripheral blood samples. In most of MRCC patients analysed (23/28), the expression of NCR (NKp46 and NKp30) was similar to that of donors. Lytic capacities by activated immunoselected NK cells from MRCC patients assessed against K562 and 3 renal tumor cell lines were in the range of that observed in NK cells from normal donors. HLA-I- renal tumor cells UOK23 were killed with a good efficiency, whereas HLA-I renal tumor cells were more resistant. Although LFA-1/ICAM-1 interaction potentiates RCC cell lysis, HLA-I/NKR interaction clearly decreased RCC cell susceptibility to NK cells. In addition, proliferation of NK cells from MRCC patients in response to cytokines was altered.

Aged↗
PubMed2003

CD158 receptor controls cytotoxic T-lymphocyte susceptibility to tumor-mediated activation-induced cell death by interfering with Fas signaling.

Renal cell carcinoma-infiltrating lymphocytes express killer cell immunoglobulin-like receptors (KIRs) that inhibit antitumor CD8+ T-cell functions and may contribute to local self-tolerance. In the present study, to better examine the functional consequences of KIR engagement on CTL-tumor interactions, we investigated the influence of KIR2DL1/CD158a on CTL survival. We show that both KIR+ and KIR- antigen-specific CTLs express Fas and Fas ligand and were susceptible to activation-induced cell death (AICD) triggered by coated anti-CD3 monoclonal antibodies. In KIR+ CTLs, anti-CD158a monoclonal antibodies partially inhibited anti-CD3-induced AICD. Interestingly, T-cell receptor activation by cognate tumor cells induced apoptosis in KIR+ CTLs but not in KIR- CTLs. In addition, co-engagement of T-cell receptors and KIRs by tumor cells decreased tumor-mediated CTL apoptosis. Blocking the interaction of KIR/HLA-Cw4 resulted in the restoration of tumor-induced AICD. Most importantly, our data indicate that KIR engagement affected two proximal events of Fas signaling pathway, a sustained c-FLIP-L induction and a decrease in caspase 8 activity. These studies provide evidence that tumor cells selectively favor the local persistence of nonfunctional KIR+ CTLs by promoting their survival.

Antibodies, Monoclonal↗
PubMed2002

Engagement of the inhibitory receptor CD158a interrupts TCR signaling, preventing dynamic membrane reorganization in CTL/tumor cell interaction.

Renal cell carcinoma (RCC) infiltrating lymphocytes (TILs) express killer cell immunoglobulinlike receptors (KIRs) that inhibit the antitumor CD8(+) T-cell lysis. In the present study, to better examine the functional consequences of KIR engagement on cytotoxic T lymphocyte (CTL)/tumor interaction, we have investigated the influence of KIR CD158a on early steps of T-cell activation. We show that coengagement of T-cell receptor (TCR) and CD158a by tumor cells inhibited tyrosine phosphorylation of early signaling proteins ZAP-70 and LAT, lipid raft coalescence, and TCR/CD3 accumulation at the CTL/tumor cell interface. In addition, the guanine exchange factor Vav was not phosphorylated, and no actin cytoskeleton rearrangement was observed. Our data indicate a role of KIR CD158a in the dynamic events induced by TCR triggering, preventing CTL membrane reorganization, and subsequent completion of CTL activation program. Accordingly, the expression of CD158 by TILs may favor tumor cell escape to the immune response.

Calcium↗
PubMedDate not supplied

[Tumor/cytotoxic effector cross-talk in the control of tumor susceptibility to lysis].

During the two least decades, the field of tumor immunology has met an expansion of knowledge about the molecular and cellular bases of immune regulation. The identification of cancer antigens has been of critical importance and cancer vaccine is at present a very fast moving field. However, the immunotherapy approaches in cancer are of modest success. This is mainly due to the capacity of tumor cells to escape from immunological detection and to resist to cell mediated cytotoxicity. We will discuss some mechanisms associated with the acquisition of this tumor resistance and the alteration of T cell function and how cancer profiling through genomics approaches may help to reconceptualize immunotherapy strategies.

Apoptosis↗