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Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer. We highlight key mechanisms which may inform cancer treatment and propose pertinent areas for future research. We suggest areas where understanding the communication between granulocytes, mast cells, and the tumor microenvironment, will be crucial for identifying immune mechanisms that may be harnessed to counteract tumor development. For example, a comprehensive understanding of allergic and immune factors driving distinct neutrophil states and those mechanisms that link mast cells with immunotherapy resistance, might enable targeted manipulation of specific subpopulations, leading to precision immunotherapy in cancer. We recommend specific areas of investigation in AllergoOncology and knowledge exchange across disease contexts to uncover pertinent reciprocal functions in allergy and cancer and allow therapeutic manipulation of these powerful cell populations. These will help address the unmet needs in stratifying and managing patients with allergic diseases and cancer. [ABSTRACT FROM AUTHOR]

B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma. B cells are playing an active role in shaping the tumour immune microenvironment and the anti-tumour immune response in melanomas. Here authors show that intra-tumoral B cells are aberrantly activated and produce antibodies that are potentially autoreactive. [ABSTRACT FROM AUTHOR]

Significant advances in the treatment of several cancers have been achieved by the introduction of immune-checkpoint blockade, however response rates are variable.[1] Immune checkpoint molecules such as programmed-death-1 (PD-1) on T cells, are crucial for balancing immune system activation thereby preventing destruction of healthy tissues. Clinical benefit from anti-PD-1 therapy, and overall survival (OS) were positively associated with lower pre-therapy T effector cell (T SB eff sb ) IRC. Anti-PD1 therapy outcome can be predicted by pre-therapy IFN-I responsiveness of Teff cells. [Extracted from the article]

Human B cells and their expressed antibodies are crucial in conferring immune protection. Identifying pathogen-specific antibodies following infection is possible due to enhanced humoral immunity against well-described molecules on the pathogen surface. However, screening for cancer-reactive antibodies remains challenging since target antigens are often not identified a priori and the frequency of circulating B cells recognizing cancer cells is likely very low. We investigated whether combined ex vivo culture of human B cells with three innate stimuli, interleukin-17 (IL-17), B-cell activation factor (BAFF), and the toll-like receptor 9 (TLR-9) agonist DNA motif CpG ODN 2006 (CpG), each known to activate B cells through different signalling pathways, promote cell activation, proliferation, and antibody production. Combined IL-17+BAFF+CpG prolonged B-cell survival and increased proliferation compared with single stimuli. IL-17+BAFF+CpG triggered higher IgG secretion, likely by activating differentiated, memory and class-switched CD19+CD20+CD27+IgD- B cells. Regardless of anti-FOLR antibody seropositive status, IL-17+BAFF+CpG combined with a monovalent tumour-associated antigen (folate receptor alpha [FOLR]) led to secreted antibodies recognizing the antigen and the antigen-expressing IGROV1 cancer cells. In a seropositive individual, FOLR stimulation favoured class-switched memory B-cell precursors (CD27-CD38-IgD-), class-switched memory B cells and anti-FOLR antibody production, while IL-17+BAFF+CpG combined with FOLR, promoted class-switched memory B-cell precursors and antibody-secreting (CD138+IgD-) plasma cells. Furthermore, IL-17+BAFF+CpG stimulation of peripheral blood B cells from patients with melanoma revealed tumour cell-reactive antibodies in culture supernatants. These findings suggest that innate signals stimulate B-cell survival and antibody production and may help identify low-frequency antigen-reactive humoral responses. [ABSTRACT FROM AUTHOR]

B cells are emerging as key players of anti-tumor adaptive immune responses. We investigated regulatory and pro-inflammatory cytokine-expressing B cells in patients with melanoma by flow cytometric intracellular cytokine, CyTOF, transcriptomic, immunofluorescence, single-cell RNA-seq, and B:T cell co-culture analyses. We found enhanced circulating regulatory (TGF-β+ and PD-L1+) and reduced pro-inflammatory TNF-α+ B cell populations in patients compared with healthy volunteers (HVs), including lower IFN-γ+:IL-4+ and higher TGF-β+:TNF-α+ B cell ratios in patients. TGF-β-expressing B cells in the melanoma tumor microenvironment assembled in clusters and interacted with T cells via lymphoid recruitment (SELL, CXCL13, CCL4, CD74) signals and with Tregs via CD47:SIRP-γ, and FOXP3-promoting Galectin-9:CD44. While reduced in tumors compared to blood, TNF-α-expressing B cells engaged in crosstalk with Tregs via TNF-α signaling and the ICOS/ICOSL axis. Patient-derived B cells promoted FOXP3+ Treg differentiation in a TGF-β-dependent manner, while sustaining expression of IFN-γ and TNF-α by autologous T-helper cells and promoting T-helper cell proliferation ex vivo, an effect further enhanced with anti-PD-1 checkpoint blockade. Our findings reveal cytokine-expressing B cell compartments skewed toward regulatory phenotypes in patient circulation and melanoma lesions, intratumor spatial localization, and bidirectional crosstalk between B and T cell subsets with immunosuppressive attributes. [ABSTRACT FROM AUTHOR]

There is increasing evidence that B cells play a significant role in the immunobiology of melanoma; however, reports of the pro- vs. antitumour roles of B cells are inconsistent. We hypothesized that advanced melanoma favours regulatory B-cell phenotypes and class switching to less effective antibody isotypes. We conducted an in-depth characterization of the circulating humoral compartment in patients with advanced stage III/IV melanoma (n = 46), compared to healthy volunteers (n = 16). Phenotyping of circulating B cells was performed using B-cell-directed mass cytometry (CyTOF); serum immunoglobulin antibody isotyping was conducted using multiplex immunoassay; and immuno-mass spectrometry was employed to screen serum IgGs for autoantibodies against > 13 000 candidate human proteins. The melanoma B-cell compartment was enriched in naïve CD21lo B cells, plasmablasts and double-negative B cells, compared to samples from healthy controls. These populations shared significant characteristics with phenotypes enriched in classical autoimmune diseases, most notably systemic lupus erythematosus (SLE). An enriched plasmablast population showed the highest median scaled expression of regulatory B-cell markers interleukin (IL)-10 and CD95 (Fas) of all B-cell populations, suggesting a potential immunosuppressive role. Consistent with an IL-10-enriched, T helper 2-biased environment, serum antibody isotyping revealed enrichment of IgG4, a less effective antibody isotype that may promote tumour propagation, in patients with melanoma, compared to healthy controls. In support of an autoreactive immune response, immuno-mass spectrometry screening of serum IgGs revealed altered autoreactivity in sera from patients with melanoma vs. with healthy control sera. Some autoantibodies were found exclusively in patients with melanoma, and these were reactive against human proteins recognized in carcinogenesis and proteins localized to the skin. Correlations between autoreactivity to tubulin cytoskeletal components and tumour burden was also identified. These findings show parallels with SLE, where one of the principal defects is an increased presence of apoptotic cell components and a breakdown of tolerance to cell-associated autoantigens. This may also suggest that localized immune reactivity in the tumour microenvironment may be reflected in an altered regulatory and autoreactive circulating humoral compartment. Our data identify distinct immature and regulatory B-cell signatures in patients with advanced melanoma that share characteristics with those reported in autoimmune diseases. Tumour-associated immune suppression may skew class switching to less effective antibody isotypes and toward regulatory B-cell phenotypes likely to favour tumour progression. [ABSTRACT FROM AUTHOR]

Byline: Shrikant. Bobade, Vinay. Kulkarni, Sudhir. Dhumne, Saurabh. Barde, Jitesh. Chauhan, Avinash. Sharma Use of midazolam infusion in mechanically ventilated patient is an established practice in critical care. In our [...]

In the extensive rice-wheat system of India, harvesting is done mostly by combines, and the paddy residues after harvesting are normally burnt, followed by irrigating the field and intensive tillage prior to sowing of next crop wheat. While in-field, retention of previous crop residues plays an important role, such as it reduces soil erosion from water and wind and increases soil organic carbon. To avoid burning of crop residues 'Happy Seeder' was developed by PAU, Ludhiana. It greatly reduces fuel consumption, crop cost establishment and the ability to sow the seed as desired after harvesting, thereby ensuring the possibility of sowing at the optimum time and reducing the irrigation needs. In the present work, five common methods (treatments) were selected for sowing of wheat, which is Tj -- No-tillage + Happy Seeder, T2 -- No-tillage + Zero till seed drill, T3 -- Reduced tillage (disc harrow with one pass) + zero till seed drill, T4 -- 1 x Cultivator + 2 x Disc harrow + Conventional seed -cum- fertilizer drill, T5 -- 2 x Cultivator + 2 x Disc harrow + Raised bed seed drill. With the use of Happy Seeder, sufficient tillage operation time was saved because the machine is used directly after harvesting of paddy field. The highest effective field capacity was found in T5 with 0.48 ha/h, highest field efficiency and seed emergence in T4 with 70.2 % & 85.7 %, respectively. Maximum grain yield was found in Tt with 42.4 q/ha and minimum in T2 with 37.8 q/ha. Plant population and highest weed density was found in T4 with 143 plants/m2 and 67, 69, 75 numbers/m2 at 30, 60 and 90 days. The weed count increased with days due to variation in degree of soil manipulation. [ABSTRACT FROM AUTHOR]

B cells are emerging as key players of anti-tumor adaptive immune responses. We investigated regulatory and pro-inflammatory cytokine-expressing B cells in patients with melanoma by flow cytometric intracellular cytokine, CyTOF, transcriptomic, immunofluorescence, single-cell RNA-seq, and B:T cell co-culture analyses. We found enhanced circulating regulatory (TGF-β + and PD-L1 + ) and reduced pro-inflammatory TNF-α + B cell populations in patients compared with healthy volunteers (HVs), including lower IFN-γ + :IL-4 +  and higher TGF-β + :TNF-α + B cell ratios in patients. TGF-β-expressing B cells in the melanoma tumor microenvironment assembled in clusters and interacted with T cells via lymphoid recruitment (SELL, CXCL13, CCL4, CD74) signals and with Tregs via CD47:SIRP-γ, and FOXP3-promoting Galectin-9:CD44. While reduced in tumors compared to blood, TNF-α-expressing B cells engaged in crosstalk with Tregs via TNF-α signaling and the ICOS/ICOSL axis. Patient-derived B cells promoted FOXP3 + Treg differentiation in a TGF-β-dependent manner, while sustaining expression of IFN-γ and TNF-α by autologous T-helper cells and promoting T-helper cell proliferation ex vivo , an effect further enhanced with anti-PD-1 checkpoint blockade. Our findings reveal cytokine-expressing B cell compartments skewed toward regulatory phenotypes in patient circulation and melanoma lesions, intratumor spatial localization, and bidirectional crosstalk between B and T cell subsets with immunosuppressive attributes., Competing Interests: S. N. Karagiannis and J. Spicer are founders and shareholders of Epsilogen Ltd. All other authors have declared that no conflict of interest exists., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)