Chemosensor receptors are lipid-detecting regulators of macrophage function in cancer.

Infiltration of macrophages into tumors is a hallmark of cancer progression, and re-educating tumor-associated macrophages (TAMs) toward an antitumor status is a promising immunotherapy strategy. However, the mechanisms through which cancer cells affect macrophage education are unclear, limiting the therapeutic potential of this approach. Here we conducted an unbiased genome-wide CRISPR screen of primary macrophages.

Isolated surgical valve replacement for tricuspid regurgitation: An international multicenter study.

Background: Although the management of tricuspid regurgitation during mitral surgery is standardized, the approach to patients with isolated tricuspid regurgitation is less clearly defined. This study examined the surgical outcomes of patients who underwent isolated surgical tricuspid valve replacement at 2 medical centers, providing insights into the postoperative and midterm outcomes.

Methods: This retrospective observational study analyzed data from 2 tertiary cardiac surgery centers.

Interplay between the complement system and other immune pathways in the tumor microenvironment.

Tumor growth and spread are sustained by the tumor microenvironment. Inflammatory cells and pathways have a fundamental role in the tumor microenvironment, driving or conditioning the functional activation of other leukocyte subsets and favoring evasion of anti-tumor immunity. One of the inflammatory pathways contributing to cancer-related inflammation is the complement system.

Monocyte-macrophage membrane expression of IL-1R2 is a severity biomarker in sepsis.

Interleukin-1 (IL-1)/IL-1 receptor family consists of activators and inhibitors which play a key role in inflammation, emergency myelopoiesis, and myeloid cell activation. The latter includes the IL-1R2 decoy receptor. To investigate the expression and significance of IL-1R2 in sepsis, we conducted high-dimensional flow cytometry of circulating cells from patients stratified according to the Sequential Sepsis-Related Organ Failure Assessment (SOFA) score.

C/EBPβ-dependent autophagy inhibition hinders NK cell function in cancer.

NK cells are endowed with tumor killing ability, nevertheless most cancers impair NK cell functionality, and cell-based therapies have limited efficacy in solid tumors. How cancers render NK cell dysfunctional is unclear, and overcoming resistance is an important immune-therapeutic aim. Here, we identify autophagy as a central regulator of NK cell anti-tumor function.

COVID-19 thromboinflammation: adding inflammatory fibrin to the puzzle.

Thromboinflammation is a peculiar and key component of acute COVID-19 pathogenesis, which contributes to long COVID. In a recent study, Ryu et al. demonstrate that the SARS-CoV-2 spike protein interacts with fibrinogen, promoting fibrin polymerization and its inflammatory activity.

BTN2A1 targeting reprograms M2-like macrophages and TAMs via SYK and MAPK signaling.

Tumor-associated macrophages (TAMs), often adopting an immunosuppressive M2-like phenotype, correlate with unfavorable cancer outcomes. Our investigation unveiled elevated expression of the butyrophilin (BTN)2A1 in M2-like TAMs across diverse cancer types. We developed anti-BTN2A1 monoclonal antibodies (mAbs), and notably, one clone demonstrated a robust inhibitory effect on M2-like macrophage differentiation, inducing a shift toward an M1-like phenotype both in vitro and ex vivo in TAMs from patients with cancer.

The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19.

Background: COVID-19 clinical course is highly variable and secondary infections contribute to COVID-19 complexity. Early detection of secondary infections is clinically relevant for patient outcome. Procalcitonin (PCT) and C-reactive protein (CRP) are the most used biomarkers of infections.

Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells.

Neutrophils are the most abundant leukocytes in human blood and play a primary role in resistance against invading microorganisms and in the acute inflammatory response. However, their role in colitis and colitis-associated colorectal cancer is still under debate. This study aims to dissect the role of neutrophils in these pathologic contexts by using a rigorous genetic approach.

Multiplexed Imaging Mass Cytometry Analysis in Preclinical Models of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. PDAC is characterized by a complex tumor microenvironment (TME), that plays a pivotal role in disease progression and resistance to therapy. Investigating the spatial distribution and interaction of TME cells with the tumor is the basis for understanding the mechanisms underlying disease progression and represents a current challenge in PDAC research.

The Yin Yang of Complement and Cancer.

Cancer-related inflammation is a crucial component of the tumor microenvironment (TME). Complement activation occurs in cancer and supports the development of an inflammatory microenvironment. Complement has traditionally been considered a mechanism of immune resistance against cancer, and its activation is known to contribute to the cytolytic effects of antibody-based immunotherapeutic treatments.

Complement activation in cancer: Effects on tumor-associated myeloid cells and immunosuppression.

Cancer-related inflammation plays a central role in the establishment of tumor-promoting mechanisms. Tumor-associated myeloid cells, which engage in complex interactions with cancer cells, as well as stromal and tumor immune infiltrating cells, promote cancer cell proliferation and survival, angiogenesis, and the generation of an immunosuppressive microenvironment. The complement system is one of the inflammatory mechanisms activated in the tumor microenvironment.

Negative Regulation of the IL-1 System by IL-1R2 and IL-1R8: Relevance in Pathophysiology and Disease.

Interleukin-1 (IL-1) is a primary cytokine of innate immunity and inflammation. IL-1 belongs to a complex family including ligands with agonist activity, receptor antagonists, and an anti-inflammatory cytokine. The receptors for these ligands, the IL-1 Receptor (IL-1R) family, include signaling receptor complexes, decoy receptors, and negative regulators.

Lipid-loaded tumor-associated macrophages sustain tumor growth and invasiveness in prostate cancer.

Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis of this correlation and therapeutic strategies to target TAMs in PCa remain poorly defined. Here, single-cell RNA sequencing was used to profile the transcriptional landscape of TAMs in human PCa, leading to identification of a subset of macrophages characterized by dysregulation in transcriptional pathways associated with lipid metabolism.

Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression.

Complement has emerged as a component of tumor promoting inflammation. We conducted a systematic assessment of the role of complement activation and effector pathways in sarcomas. , and mice showed reduced susceptibility to 3-methylcholanthrene sarcomagenesis and transplanted sarcomas, whereas C1q and factor B deficiency had marginal effects.

Noncanonical Functions of C1s Complement Its Canonical Functions in Renal Cancer.

Complement activation contributes to tumor progression in several cancer types. In this issue, Daugan and colleagues propose complement component C1s and C4d as new markers of prognosis in clear cell renal cell carcinoma. The mechanism of action of C1s involves both canonical and intracellular, noncanonical functions.

Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus.

Serum amyloid P component (SAP, also known as Pentraxin 2; APCS gene) is a component of the humoral arm of innate immunity involved in resistance to bacterial infection and regulation of tissue remodeling. Here we investigate the role of SAP in antifungal resistance. Apcs mice show enhanced susceptibility to A.

Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.

Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using a genetic approach complemented by adoptive transfer, we found that neutrophils are essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. Neutrophils were essential for the activation of an interferon-γ-dependent pathway of immune resistance, associated with polarization of a subset of CD4 CD8 unconventional αβ T cells (UTC).

The requirements for manufacturing highly active or sensitising drugs comparing Good Manufacturing Practices.

Background: To date there exist no internationally recognised Good Manufacturing Practices (GMP) that clearly outline universally accepted standards for manufacturing highly active or sensitising ingredients. The pharmaceutical industry is faced with a twofold problem: determining which drugs need dedicated production areas and identifying the different regulations required in different countries. The aim of this paper is to find, by comparing the current regulations of the various Regulatory Agencies, the differences between containment requirements for the production of highly active or sensitising ingredients.

The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer.

The innate immune system comprises a cellular and a humoral arm. Humoral pattern recognition molecules include complement components, collectins, ficolins, and pentraxins. These molecules are involved in innate immune responses by recognizing microbial moieties and damaged tissues, activating complement, exerting opsonic activity and facilitating phagocytosis, and regulating inflammation.

PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer.

Innate immunity includes a cellular and a humoral arm. PTX3 is a fluid-phase pattern recognition molecule conserved in evolution which acts as a key component of humoral innate immunity in infections of fungal, bacterial, and viral origin. PTX3 binds conserved microbial structures and self-components under conditions of inflammation and activates effector functions (complement, phagocytosis).