Immune cell networking in solid tumors: focus on macrophages and neutrophils.

The tumor microenvironment is composed of tumor cells, stromal cells and leukocytes, including innate and adaptive immune cells, and represents an ecological niche that regulates tumor development and progression. In general, inflammatory cells are considered to contribute to tumor progression through various mechanisms, including the formation of an immunosuppressive microenvironment. Macrophages and neutrophils are important components of the tumor microenvironment and can act as a double-edged sword, promoting or inhibiting the development of the tumor.

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.

Neutrophil diversity in inflammation and cancer.

Neutrophils are the most abundant circulating leukocytes in humans and the first immune cells recruited at the site of inflammation. Classically perceived as short-lived effector cells with limited plasticity and diversity, neutrophils are now recognized as highly heterogenous immune cells, which can adapt to various environmental cues. In addition to playing a central role in the host defence, neutrophils are involved in pathological contexts such as inflammatory diseases and cancer.

Stromal and Immune Cell Dynamics in Tumor Associated Tertiary Lymphoid Structures and Anti-Tumor Immune Responses.

Tertiary lymphoid structures (TLS) are ectopic lymphoid organs that have been observed in chronic inflammatory conditions including cancer, where they are thought to exert a positive effect on prognosis. Both immune and non-immune cells participate in the genesis of TLS by establishing complex cross-talks requiring both soluble factors and cell-to-cell contact. Several immune cell types, including T follicular helper cells (Tfh), regulatory T cells (Tregs), and myeloid cells, may accumulate in TLS, possibly promoting or inhibiting their development.

Chemokines as Regulators of Neutrophils: Focus on Tumors, Therapeutic Targeting, and Immunotherapy.

Neutrophils are an important component of the tumor microenvironment, and their infiltration has been associated with a poor prognosis for most human tumors. However, neutrophils have been shown to be endowed with both protumor and antitumor activities, reflecting their heterogeneity and plasticity in cancer. A growing body of studies has demonstrated that chemokines and chemokine receptors, which are fundamental regulators of neutrophils trafficking, can affect neutrophil maturation and effector functions.

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.

Tumor-associated myeloid cells: diversity and therapeutic targeting.

Myeloid cells in tumor tissues constitute a dynamic immune population characterized by a non-uniform phenotype and diverse functional activities. Both tumor-associated macrophages (TAMs), which are more abundantly represented, and tumor-associated neutrophils (TANs) are known to sustain tumor cell growth and invasion, support neoangiogenesis and suppress anticancer adaptive immune responses. In recent decades, several therapeutic approaches have been implemented in preclinical cancer models to neutralize the tumor-promoting roles of both TAMs and TANs.

The complexity of neutrophils in health and disease: Focus on cancer.

Neutrophils are essential soldiers of the immune response and their role have long been restricted to their activities in defence against microbial infections and during the acute phase of the inflammatory response. However, increasing number of investigations showed that neutrophils are endowed with plasticity and can participate in the orchestration of both innate and adaptive immune responses. Neutrophils have an impact on a broad range of disorders, including infections, chronic inflammations, and cancer.

Neutrophil diversity and plasticity in tumour progression and therapy.

Neutrophils play a key role in defence against infection and in the activation and regulation of innate and adaptive immunity. In cancer, tumour-associated neutrophils (TANs) have emerged as an important component of the tumour microenvironment. Here, they can exert dual functions.

Impact of RAS mutations on the immune infiltrate of colorectal liver metastases: A preliminary study.

Kirsten rat sarcoma viral oncogene homolog KRAS proto-oncogene is the most common altered gene in colorectal cancer (CRC). Determining its mutational status, which is associated with worse prognosis and resistance to anti-epidermal growth factor receptor (EGFR) inhibitors, is essential for managing patients with CRC and colon liver metastases (CLM). Emerging studies highlighted the relationship of KRAS-mutated cancers and tumor microenvironment components, mainly with T cells.

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).

Innate immunity, inflammation and tumour progression: double-edged swords.

Components of the cellular and the humoral arm of the immune system are essential elements of the tumour microenvironment (TME). The TME includes tumour-associated macrophages which have served as a paradigm for the cancer-promoting inflammation. Cytokines, IL-1 in particular, and complement have emerged as important players in tumour promotion.

Role of a fluid-phase PRR in fighting an intracellular pathogen: PTX3 in Shigella infection.

Shigella spp. are pathogenic bacteria that cause bacillary dysentery in humans by invading the colonic and rectal mucosa where they induce dramatic inflammation. Here, we have analyzed the role of the soluble PRR Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity.

Dissecting neutrophil complexity in cancer.

Neutrophils represent the most abundant leukocyte population in human peripheral blood, and their role had long been considered restricted to their phagocytic and antimicrobial activities during the acute phase of inflammation. However, an increasing number of recent investigations had highlighted their possible impact in tumor initiation and development, and the nature of neutrophil contribution in cancer had become a hot topic in immunology. Over the years, neutrophils have been shown to display both pro-tumor and antitumor effects, emphasizing an unexpected cellular heterogeneity in cancer.

IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity.

Interleukin-1 receptor 8 (IL-1R8, also known as single immunoglobulin IL-1R-related receptor, SIGIRR, or TIR8) is a member of the IL-1 receptor (ILR) family with distinct structural and functional characteristics, acting as a negative regulator of ILR and Toll-like receptor (TLR) downstream signalling pathways and inflammation. Natural killer (NK) cells are innate lymphoid cells which mediate resistance against pathogens and contribute to the activation and orientation of adaptive immune responses. NK cells mediate resistance against haematopoietic neoplasms but are generally considered to play a minor role in solid tumour carcinogenesis.

Sexual Dimorphism in Innate Immunity.

Sexual dimorphisms account for differences in clinical manifestations or incidence of infectious or autoimmune diseases and malignancy between females and males. Females develop enhanced innate and adaptive immune responses than males and are less susceptible to many infections of bacterial, viral, parasitic, and fungal origin and malignancies but in contrast, they are more prone to develop autoimmune diseases. The higher susceptibility to infections in males is observed from birth to adulthood, suggesting that sex chromosomes and not sex hormones have a major role in sexual dimorphism in innate immunity.

Anti-pentraxin antibodies in autoimmune systemic diseases: Focus on anti-pentraxin-3 autoantibodies.

Pentraxins are soluble pattern recognition molecules implicated not only in the opsonization and removal of microorganisms but also in the clearance of modified self (i.e., dying cells).

Interplay between Myeloid Cells and Humoral Innate Immunity.

The innate immune system represents the first line of defense against pathogens and comprises both a cellular and a humoral arm. Fluid-phase pattern recognition molecules (PRMs), which include collectins, ficolins, and pentraxins, are key components of the humoral arm of innate immunity and are expressed by a variety of cells, including myeloid, epithelial, and endothelial cells, mainly in response to infectious and inflammatory conditions. Soluble PRMs share basic multifunctional properties including activation and regulation of the complement cascade, opsonization of pathogens and apoptotic cells, regulation of leukocyte extravasation, and fine-tuning of inflammation.

Fluid phase recognition molecules in neutrophil-dependent immune responses.

The innate immune system comprises both a cellular and a humoral arm. Neutrophils are key effector cells of the immune and inflammatory responses and have emerged as a major source of humoral pattern recognition molecules (PRMs). These molecules, which include collectins, ficolins, and pentraxins, are specialised in the discrimination of self versus non-self and modified-self and share basic multifunctional properties including recognition and opsonisation of pathogens and apoptotic cells, activation and regulation of the complement cascade and tuning of inflammation.

Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer.

Inflammatory cells are an essential component of the tumor microenvironment. Neutrophils have emerged as important players in the orchestration and effector phase of innate and adaptive immunity. The significance of tumor-associated neutrophils (TAN) in colorectal cancer (CRC) has been the subject of conflicting reports and the present study was designed to set up a reliable methodology to assess TAN infiltration in CRC and to evaluate their clinical significance.