Emerging evidence suggests an immunosuppressive role of altered tumor glycosylation due to downregulation of innate immune responses via immunoregulatory Siglecs. In contrast, human T cells, a major anticancer effector cell, only rarely express Siglecs. However, here, we report that the majority of intratumoral, but not peripheral blood, cytotoxic CD8 þ T cells expressed Siglec-9 in melanoma. We identified Siglec-9 þ CD8 þ T cells as a subset of effector memory cells with high functional capacity and signatures of clonal expansion. This cytotoxic T-cell subset was functionally inhibited in the presence of Siglec-9 ligands or by Siglec-9 engagement by specific antibodies. TCR signaling pathways and key effector functions (cytotoxicity, cytokine production) of CD8 þ T cells were suppressed by Siglec-9 engagement, which was associated with the phosphorylation of the inhibitory protein tyrosine phosphatase SHP-1, but not SHP-2. Expression of cognate Siglec-9 ligands was observed on the majority of tumor cells in primary and metastatic melanoma specimens. Targeting the tumor-restricted, glycosylation-dependent Siglec-9 axis may unleash this intratumoral T-cell subset, while confining T-cell activation to the tumor microenvironment.

Aberrant glycosylation is a key feature of malignant transformation. Hypersialylation, the enhanced expression of sialic acid-terminated glycoconjugates on the cell surface, has been linked to immune evasion and metastatic spread, eventually by interaction with sialoglycan-binding lectins, including Siglecs and selectins. The biosynthesis of tumor-associated sialoglycans involves sialyltransferases, which are differentially expressed in cancer cells. In this review article, we provide an overview of the twenty human sialyltransferases and their roles in cancer biology and immunity. A better understanding of the individual contribution of select sialyltransferases to the tumor sialome may lead to more personalized strategies for the treatment of cancer.

Background Identifying and removing reference duplicates when conducting systematic reviews (SRs) remain a major, time-consuming issue for authors who manually check for duplicates using built-in features in citation managers. To address issues related to manual deduplication, we developed an automated, efficient, and rapid artificial intelligence-based algorithm named Deduklick. Deduklick combines natural language processing algorithms with a set of rules created by expert information specialists. Methods Deduklick’s deduplication uses a multistep algorithm of data normalization, calculates a similarity score, and identifies unique and duplicate references based on metadata fields, such as title, authors, journal, DOI, year, issue, volume, and page number range. We measured and compared Deduklick’s capacity to accurately detect duplicates with the information specialists’ standard, manual duplicate removal process using EndNote on eight existing heterogeneous datasets. Using a sensitivity analysis, we manually cross-compared the efficiency and noise of both methods. Discussion Deduklick achieved average recall of 99.51%, average precision of 100.00%, and average F1 score of 99.75%. In contrast, the manual deduplication process achieved average recall of 88.65%, average precision of 99.95%, and average F1 score of 91.98%. Deduklick achieved equal to higher expert-level performance on duplicate removal. It also preserved high metadata quality and drastically reduced time spent on analysis. Deduklick represents an efficient, transparent, ergonomic, and time-saving solution for identifying and removing duplicates in SRs searches. Deduklick could therefore simplify SRs production and represent important advantages for scientists, including saving time, increasing accuracy, reducing costs, and contributing to quality SRs.

While inhibitory Siglec receptors are known to regulate myeloid cells, less is known about their expression and function in lymphocytes subsets. Here we identified Siglec-7 as a glyco-immune checkpoint expressed on non-exhausted effector memory CD8+ T cells that exhibit high functional and metabolic capacities. Seahorse analysis revealed higher basal respiration and glycolysis levels of Siglec-7+ CD8+ T cells in steady state, and particularly upon activation. Siglec-7 polarization into the T cell immune synapse was dependent on sialoglycan interactions in trans and prevented actin polarization and effective T cell responses. Siglec-7 ligands were found to be expressed on both leukemic stem cells and acute myeloid leukemia (AML) cells suggesting the occurrence of glyco-immune checkpoints for Siglec-7+ CD8+ T cells, which were found in patients’ peripheral blood and bone marrow. Our findings project Siglec-7 as a glyco-immune checkpoint and therapeutic target for T cell-driven disorders and cancer.

Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche and fundamental regulators of homeostasis and regeneration. We interrogated their function during virus-induced lung injury using the highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. We applied complementary approaches with primary pediatric LR-MSCs and a state-of-the-art model of human RSV infection in lamb. Remarkably, RSV-infection of pediatric LR-MSCs led to a robust activation, characterized by a strong antiviral and pro-inflammatory phenotype combined with mediators related to T cell function. In line with this, following in vivo infection, RSV invades and activates LR-MSCs, resulting in the expansion of the pulmonary MSC pool. Moreover, the global transcriptional response of LR-MSCs appears to follow RSV disease, switching from an early antiviral signature to repair mechanisms including differentiation, tissue remodeling, and angiogenesis. These findings demonstrate the involvement of LR-MSCs during virus-mediated acute lung injury and may have therapeutic implications.