Tissue-specific immunosuppressive and proliferating macrophages fuel early metastatic progression of human colorectal cancer to liver.

Early synchronous colorectal liver metastasis (CRLM) represents a clinical condition characterized by the simultaneous presence of primary colorectal cancer (CRC) and metastatic liver lesions. In this study, we characterized the tissue-specific transcriptomes, phenotypes, and functional relevance of tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) of CRC and CRLM specimens from patients who underwent simultaneous surgical removal of these malignancies. The high-throughput single-cell transcriptional analysis revealed an inverse ratio of inflammatory and immunoregulatory TAMs in the CRC and CRLM TMEs, along with heterogeneity in both tumoral tissues.

Immune evasion mechanisms in early-stage I high-grade serous ovarian carcinoma: insights into regulatory T cell dynamics.

The mechanisms driving immune evasion in early-stage I high-grade serous ovarian carcinoma (HGSOC) remain poorly understood. To investigate this, we performed single-cell RNA-sequencing analysis. Our findings revealed a highly immunosuppressive HGSOC microenvironment, characterized by abundant infiltration of regulatory T cells (Tregs).

Expansion of memory Vδ2 T cells following SARS-CoV-2 vaccination revealed by temporal single-cell transcriptomics.

γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response.

Perioperative corticosteroid treatment impairs tumor-infiltrating dendritic cells in patients with newly diagnosed adult-type diffuse gliomas.

Introduction: Adult-type diffuse gliomas are malignant primary brain tumors characterized by very poor prognosis. Dendritic cells (DCs) are key in priming antitumor effector functions in cancer, but their role in gliomas remains poorly understood.

Methods: In this study, we characterized tumor-infiltrating DCs (TIDCs) in adult patients with newly diagnosed diffuse gliomas by using multi-parametric flow cytometry and single-cell RNA sequencing.

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19.

Monocytes are critical cells of the immune system but their role as effectors is relatively poorly understood, as they have long been considered only as precursors of tissue macrophages or dendritic cells. Moreover, it is known that this cell type is heterogeneous, but our understanding of this aspect is limited to the broad classification in classical/intermediate/non-classical monocytes, commonly based on their expression of only two markers, i.e.

Intrahepatic CD69Vδ1 T cells re-circulate in the blood of patients with metastatic colorectal cancer and limit tumor progression.

Background: More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack of reliable prognostic markers. Vδ1 cells are a subset of tissue-resident gamma delta (γδ) T lymphocytes endowed with a broad array of antitumor functions and showing a natural high tropism for the liver. However, little is known about their impact in the clinical outcomes of CLM.

Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications.

Natural Killer (NK) cells are lymphocytes of the innate immunity that play a crucial role in the control of viral infections in the absence of a prior antigen sensitization. Indeed, they display rapid effector functions against target cells with the capability of direct cell killing and antibody-dependent cell-mediated cytotoxicity. Furthermore, NK cells are endowed with immune-modulatory functions innate and adaptive immune responses the secretion of chemokines/cytokines and by undertaking synergic crosstalks with other innate immune cells, including monocyte/macrophages, dendritic cells and neutrophils.

NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions.

Human Vδ2 cells are innate-like γδ T effectors performing potent immune surveillance against tumors. The constitutive expression of NKG2A identifies a subset of Vδ2 T cells licensed with an intrinsic hyper-responsiveness against cancer. Indeed, the transcriptomic profiles of NKG2A and NKG2A cells characterize two distinct "intralineages" of Vδ2 T lymphocytes that appear early during development, keep their phenotypes, and show self-renewal capabilities in adult life.

Molecular Recognition between Cadherins Studied by a Coarse-Grained Model Interacting with a Coevolutionary Potential.

Studying the conformations involved in the dimerization of cadherins is highly relevant to understand the development of tissues and its failure, which is associated with tumors and metastases. Experimental techniques, like X-ray crystallography, can usually report only the most stable conformations, missing minority states that could nonetheless be important for the recognition mechanism. Computer simulations could be a valid complement to the experimental approach.