Biology subjects

Lucca, L. E.

Publications and source records attributed to Lucca, L. E..

3 recordsLinked to original sources

bioRxiv2024

Inflamed Natural Killer cells with adhesion defects are associated with a poor prognosis in Multiple Myeloma

The promising results obtained with immunotherapeutic approaches for multiple myeloma (MM) call for a better stratification of patients based on immune components. The most pressing being cytotoxic lymphocytes such as Natural Killer (NK) cells that are mandatory for MM surveillance and therapy. In this study, we performed a single cell RNA sequencing analysis of NK cells from 10 MM patients and 10 age/sex matched healthy donors (HD) that revealed important transcriptomic changes in NK cell landscape affecting both the bone marrow and peripheral blood compartment. The frequency of mature cytotoxic "CD56dim" NK cell subsets was reduced in MM patients at the advantage of late-stage NK cell subsets expressing NF{kappa}B and IFN-I inflammatory signatures. These NK cell subsets accumulating in MM patients were characterized by a low CD16 and CD226 expression and poor cytotoxic functions. MM CD16/CD226lo NK cells also had adhesion defects with reduced LFA-1 integrin activation and actin polymerization that may account for their limited effector functions in vitro. Finally, analysis of BM infiltrating NK cells in a retrospective cohort of 177 MM patients from the IFM 2009 trial demonstrated that a high frequency of NK cells and their low CD16 and CD226 expression were associated with a shorter overall survival. Thus, CD16/CD226lo NK cells with reduced effector functions accumulate along MM development and negatively impact patients clinical outcome. Given the growing interest in harnessing NK cells to treat myeloma, this improved knowledge around MM-associated NK cell dysfunction will stimulate the development of more efficient immunotherapeutic drugs against MM. Scientific category: Lymphoid Neoplasia; Immunobiology and Immunotherapy. KEY POINTSO_LIMM patients have increased CD16/CD226low NK cell subsets characterized by "inflammatory" signatures and reduced effector functions. C_LIO_LIThe frequency of CD16/CD226low NK cells correlate with MM patient clinical outcome C_LI

immunology↗

bioRxiv2020

Circulating Clonally Expanded T Cells Reflect Functions of Tumor Infiltrating T Cells

Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCR{beta} and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCR{beta} repertoire of circulating and tumor-infiltrating T cells were analyzed from matched tumor and blood from patients with metastatic melanoma at the single cell level. We found that in circulating T cells matching clonally expanded tumor-infiltrating T cells (circulating TILs), gene signatures of effector functions, but not terminal exhaustion, reflect those observed in the tumor. In contrast, features of exhaustion are displayed predominantly by T cells present only in tumor. Finally, genes associated with a high degree of blood-tumor TCR sharing were overexpressed in tumor tissue after immunotherapy. These data demonstrate that circulating TILs, identified by TCRs shared with T cells in tumors, have unique transcriptional expression patterns that may have utility for the interrogation of T cell function in cancer immunotherapy. SummaryCombining transcriptomic and TCR{beta} repertoire analysis of circulating and tumor-infiltrating CD8 T cells from patients with metastatic melanoma, we identify a blood-based population with effector properties that reflect those of clonally related tumor-resident T cells.

immunology↗

bioRxiv2019

Differential expression of the T cell inhibitor TIGIT in Glioblastoma and Multiple Sclerosis

To identify co-inhibitory immune pathways important in the brain, we hypothesized that comparison of T cells in lesions from patients with MS with tumor infiltrating T cells (TILs) from patients with GBM may reveal novel targets for immunotherapy. Focusing on PD-1 and TIGIT, we found that TIGIT and its ligand CD155 were highly expressed on GBM TILs but were near-absent in MS lesions, while lymphocytic expression of PD-1/PDL-1 was comparable. TIGIT was also upregulated in peripheral lymphocytes in GBM, suggesting recirculation of TILs. These data raise the possibility that anti-TIGIT therapy may be beneficial for patients with glioblastoma.

immunology↗