Crosslinking of Ly6a metabolically reprograms CD8 T cells for cancer immunotherapy.

T cell inhibitory mechanisms prevent autoimmune reactions, while cancer immunotherapy aims to remove these inhibitory signals. Chronic ultraviolet (UV) exposure attenuates autoimmunity through promotion of poorly understood immune-suppressive mechanisms. Here we show that mice with subcutaneous melanoma are not responsive to anti-PD1 immunotherapy following chronic UV irradiation, given prior to tumor injection, due to the suppression of T cell killing ability in skin-draining lymph nodes.

Nephron-Specific Overexpression Triggers Severe Inflammatory Response and Kidney Damage.

The RNA-binding proteins LIN28A and LIN28B contribute to a variety of developmental biological processes. Dysregulation of and expression is associated with numerous types of tumors. This study demonstrates that overexpression in the mouse nephrons leads to severe inflammation and kidney damage rather than to tumorigenesis.

Spatial adaptation of eosinophils and their emerging roles in homeostasis, infection and disease.

Eosinophils are bone marrow-derived granulocytes that are traditionally associated with type 2 immune responses, such as those that occur during parasite infections and allergy. Emerging evidence demonstrates the remarkable functional plasticity of this elusive cell type and its pleiotropic functions in diverse settings. Eosinophils broadly contribute to tissue homeostasis, host defence and immune regulation, predominantly at mucosal sites.

Eosinophils exhibit a unique transcriptional signature and increased sensitivity to IL-3-induced activation in response to colorectal cancer cells.

Eosinophils have been mainly studied in allergic diseases and parasitic infections. Nonetheless, eosinophils accumulate in a variety of solid tumors, including colorectal cancer, where their presence is associated with improved prognosis. Eosinophils can promote antitumor immunity through various mechanisms, including direct cytotoxicity toward tumor cells and promoting T-cell activation.

A Mouse Model for Eosinophilic Esophagitis (EoE).

Eosinophilic esophagitis (EoE) is an emerging chronic T helper type 2 (Th2)-associated, allergic, and immune-mediated disease, characterized histologically by eosinophil-predominant mucosal inflammation and clinically by esophageal dysfunction. Over the past years, the prevalence of EoE has dramatically increased globally. Until recently, most studies of EoE focused on using human biopsies, which are also used for diagnostic purposes, or esophageal epithelial cell lines, which led to major advances in the understanding of EoE.

Tuft cells and fibroblasts promote thymus regeneration through ILC2-mediated type 2 immune response.

The thymus is a primary lymphoid organ that is essential for the establishment of adaptive immunity through generation of immunocompetent T cells. In response to various stress signals, the thymus undergoes acute but reversible involution. However, the mechanisms governing its recovery are incompletely understood.

Adaptive immune response to BNT162b2 mRNA vaccine in immunocompromised adolescent patients.

Protective immunity against COVID-19 is orchestrated by an intricate network of innate and adaptive anti-viral immune responses. Several vaccines have been rapidly developed to combat the destructive effects of COVID-19, which initiate an immunological cascade that results in the generation of neutralizing antibodies and effector T cells towards the SARS-CoV-2 spike protein. Developing optimal vaccine-induced anti-SARS- CoV-2 protective immunity depends on a fully competent immune response.

CD300b regulates intestinal inflammation and promotes repair in colitis.

Chronic inflammation is a hallmark charataristic of various inflammatory diseases including inflammatory bowel disease. Subsequently, current therapeutic approaches target immune-mediated pathways as means for therapeutic intervention and promotion of mucosal healing and repair. Emerging data demonstrate important roles for CD300 receptor family members in settings of innate immunity as well as in allergic and autoimmune diseases.

T cell-eosinophil crosstalk-A new road for effective immune checkpoint blockade in breast cancer?

Immune checkpoint blockade (ICB) has revolutionized the landscape of cancer treatment. Nevertheless, most cancer patients still do not respond to ICB. In this issue of Cancer Cell, Blomberg et al.

Differential regulation of Type 1 and Type 2 mouse eosinophil activation by apoptotic cells.

Eosinophils are multifunctional, evolutionary conserved leukocytes that are involved in a plethora of responses ranging from regulation of tissue homeostasis, host defense and cancer. Although eosinophils have been studied mostly in the context of Type 2 inflammatory responses, it is now evident that they participate in Type 1 inflammatory responses and can respond to Type 1 cytokines such as IFN-γ. Notably, both Type 1- and Type 2 inflammatory environments are characterized by tissue damage and cell death.

Changes in peripheral blood eosinophils may predict colorectal cancer - A retrospective study.

Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Eosinophils are traditionally associated and studied in context of allergic diseases. However, recent data implicate their involvement in mucosal tumors, especially in CRC where they may have an anti-tumorigenic function.

Epithelial cell-expressed type II IL-4 receptor mediates eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic, food-driven allergic disease, characterized by eosinophil-rich inflammation in the esophagus. The histopathological and clinical features of EoE have been attributed to overproduction of the type 2 cytokines IL-4 and IL-13, which mediate profound alterations in the esophageal epithelium and neutralizing of their shared receptor component (IL-4Rα) with a human antibody drug (dupilumab) demonstrates clinical efficacy. Yet, the relative contribution of IL-4 and IL-13 and whether the type II IL-4 receptor (comprised of the IL-4Rα chain in association with IL-13Rα1) mediates this effect has not been determined.

Eosinophil-lymphocyte interactions in the tumor microenvironment and cancer immunotherapy.

Eosinophils are important effector cells and therapeutic targets in allergic diseases. Emerging data indicate that eosinophils infiltrate a variety of solid tumor types and have pleiotropic activities by at least two non-mutually exclusive mechanisms: direct interactions with tumor cells, and intricate cross-talk with lymphocytes. In light of the immune checkpoint inhibition revolution in cancer therapy, we review eosinophil-lymphocyte interactions in the tumor microenvironment.

Transcriptional Profiling of Mouse Eosinophils Identifies Distinct Gene Signatures Following Cellular Activation.

Eosinophils are multifunctional, evolutionary conserved leukocytes that are involved in a plethora of responses ranging from regulation of tissue homeostasis to host defense and cancer. Eosinophils have been studied mostly in the context of Type 2 inflammatory responses such as those found in allergy. Nonetheless, it is now evident that they participate in Type 1 inflammatory responses and can respond to Type 1 cytokines such as IFN-γ.

Eosinophils in Health and Disease: A State-of-the-Art Review.

Eosinophils play a homeostatic role in the body's immune responses. These cells are involved in combating some parasitic, bacterial, and viral infections and certain cancers and have pathologic roles in diseases including asthma, chronic rhinosinusitis with nasal polyps, eosinophilic gastrointestinal disorders, and hypereosinophilic syndromes. Treatment of eosinophilic diseases has traditionally been through nonspecific eosinophil attenuation by use of glucocorticoids.

Metastasis-Entrained Eosinophils Enhance Lymphocyte-Mediated Antitumor Immunity.

The recognition of the immune system as a key component of the tumor microenvironment (TME) led to promising therapeutics. Because such therapies benefit only subsets of patients, understanding the activities of immune cells in the TME is required. Eosinophils are an integral part of the TME especially in mucosal tumors.

PIR-B Regulates CD4 IL17a T-Cell Survival and Restricts T-Cell-Dependent Intestinal Inflammatory Responses.

Background & Aims: CD4 T cells are regulated by activating and inhibitory cues, and dysregulation of these proper regulatory inputs predisposes these cells to aberrant inflammation and exacerbation of disease. We investigated the role of the inhibitory receptor paired immunoglobulin-like receptor B (PIR-B) in the regulation of the CD4 T-cell inflammatory response and exacerbation of the colitic phenotype.

Methods: We used Il10 spontaneous and CD4CD45RB T-cell transfer models of colitis with PIR-B-deficient (Pirb) mice.

Innate immune cells in the tumor microenvironment.

The tumor immune microenvironment (TIME) is a complex ecosystem that contains adaptive and innate immune cells that have tumor-promoting and anti-tumor effects. There is still much to learn about the diversity, plasticity, and functions of innate immune cells in the TIME and their roles in determining the response to immunotherapies. Experts discuss recent advances in our understanding of their biology in cancer as well as outstanding questions and potential therapeutic avenues.

Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma.

Group 2 innate lymphoid cells (ILC2s) are essential to maintain tissue homeostasis. In cancer, ILC2s can harbor both pro-tumorigenic and anti-tumorigenic functions, but we know little about their underlying mechanisms or whether they could be clinically relevant or targeted to improve patient outcomes. Here, we found that high ILC2 infiltration in human melanoma was associated with a good clinical prognosis.

BNT162b2 vaccination effectively prevents the rapid rise of SARS-CoV-2 variant B.1.1.7 in high-risk populations in Israel.

Since the emergence of the SARS-CoV-2 pandemic, various genetic variants have been described. The B.1.

Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature.

Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease.

Analysis of Mouse Eosinophil Migration and Killing of Tumor Cells.

Eosinophils are bone marrow-derived cells that differentiate in the bone marrow and migrate into the peripheral blood primarily under the regulation of interleukin (IL)-5. Despite the fact that eosinophils have been mostly studied in the context of allergic inflammatory diseases, eosinophils accumulate in multiple tumors. In fact, recent data highlight key anti-tumorigenic activities for eosinophils.